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Trial record 1 of 1 for:    NCT01720524
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A Study To Evaluate Safety And Efficacy Of IV Sildenafil In The Treatment Of Neonates With Persistent Pulmonary Hypertension Of The Newborn

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ClinicalTrials.gov Identifier: NCT01720524
Recruitment Status : Completed
First Posted : November 2, 2012
Results First Posted : March 25, 2020
Last Update Posted : November 27, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Hypertension, Familial Persistent, of the Newborn
Interventions Drug: placebo
Drug: iv sildenafil
Enrollment 59
Recruitment Details This study is planned to be conducted in two parts Part A (double-blind phase) and Part B (long-term, non-intervention phase). Currently reported final results are only for Part A, at primary completion date. Part B (ongoing) results shall be provided at the time of study completion date.
Pre-assignment Details Neonates with persistent pulmonary hypertension of the newborn (PPHN) or hypoxic respiratory failure (HRF) and at risk of PPHN who were receiving inhaled nitric oxide (iNO) treatment were evaluated in this study.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study. Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Period Title: Part A
Started 29 30
Completed 22 18
Not Completed 7 12
Reason Not Completed
Insufficient Clinical Response             2             4
Adverse Event             2             2
Death             2             1
Lost to Follow-up             0             1
Missed 28 day follow-up visit             1             1
Withdrawal by Subject             0             1
Other             0             1
Lost to Follow-up             0             1
Period Title: Part B
Started 27 [1] 26 [1]
Completed 20 12
Not Completed 7 14
Reason Not Completed
Ongoing             3             5
Withdrawal by Subject             1             4
Other             2             0
Lost to Follow-up             1             3
Death             0             2
[1]
Participants who did not complete Part A could also participate in Part B.
Arm/Group Title IV Sildenafil Placebo Total
Hide Arm/Group Description Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study. Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study. Total of all reporting groups
Overall Number of Baseline Participants 29 30 59
Hide Baseline Analysis Population Description
Safety population included all participants treated with study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 29 participants 30 participants 59 participants
1.7  (0.90) 1.9  (0.75) 1.8  (0.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 30 participants 59 participants
Female
13
  44.8%
13
  43.3%
26
  44.1%
Male
16
  55.2%
17
  56.7%
33
  55.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 30 participants 59 participants
Hispanic or Latino
3
  10.3%
0
   0.0%
3
   5.1%
Not Hispanic or Latino
23
  79.3%
29
  96.7%
52
  88.1%
Unknown or Not Reported
3
  10.3%
1
   3.3%
4
   6.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 30 participants 59 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   6.9%
5
  16.7%
7
  11.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   3.4%
7
  23.3%
8
  13.6%
White
19
  65.5%
16
  53.3%
35
  59.3%
More than one race
3
  10.3%
1
   3.3%
4
   6.8%
Unknown or Not Reported
4
  13.8%
1
   3.3%
5
   8.5%
1.Primary Outcome
Title Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure
Hide Description Time in days, on iNO treatment, for participants without iNO treatment failure, was calculated 14 days from the initiation of IV study drug or hospital discharge, whichever occurred first. iNO treatment failure was defined as need for additional treatment targeting PPHN, need for extra corporeal membrane oxygenation (ECMO), or death during the study.
Time Frame 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population (ITT) included all randomized participants treated with study treatment. Here "Overall number of participants analyzed" signifies number of participants without iNO treatment failure.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 21 24
Least Squares Mean (95% Confidence Interval)
Unit of Measure: days
4.1
(2.58 to 5.58)
4.1
(2.70 to 5.50)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9850
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square (LS) mean difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-2.08 to 2.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.02
Estimation Comments [Not Specified]
2.Primary Outcome
Title Treatment Failure Rate
Hide Description Treatment failure rate was defined as percentage of participants who needed additional treatment targeting PPHN, needed ECMO, or died during the study.
Time Frame 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants treated with study treatment.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
27.6
(11.3 to 43.9)
20.0
(5.7 to 34.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4935
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 7.6
Confidence Interval (2-Sided) 95%
-14.1 to 29.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation
Hide Description Time in days, from initiation of IV study drug to final weaning of mechanical ventilation among participants achieving final weaning of mechanical ventilation for PPHN was evaluated. Kaplan-Meier method was used for estimation. For subjects with mechanical ventilation beyond 336 hours (14 days) from initiation of IV study drug, data was censored at 14 days.
Time Frame 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants treated with study treatment.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Median (95% Confidence Interval)
Unit of Measure: days
8.3
(5.46 to 11.75)
7.3
(5.46 to 10.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9885
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure
Hide Description Time in days, from initiation of IV study drug to first treatment failure (defined as need for additional treatment targeting PPHN, need for ECMO, or death) for participants with treatment failure was evaluated. Kaplan-Meier method was used for estimation. For participants without treatment failure by the endpoint assessment date, data was censored at the endpoint assessment date.
Time Frame 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants treated with study treatment.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Due to low number of participants with events, Kaplan-Meier estimates of median, upper and lower limit of CI could not be estimated/calculated.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4910
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Individual Components of Treatment Failure
Hide Description Percentage of participants with individual components of treatment failure (need to start additional treatment targeting PPHN, need to start ECMO, or death) were evaluated. Some participants could have had multiple qualifying events for treatment failure.
Time Frame 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants treated with study treatment.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Additional Treatment Targeting PPHN
13.8
(3.9 to 31.7)
10.0
(2.1 to 26.5)
ECMO
10.3
(2.2 to 27.4)
10.0
(2.1 to 26.5)
Death
6.9
(0.8 to 22.8)
0.0
(0.0 to 11.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Additional Treatment
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7065
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-15.2 to 22.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments ECMO
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-18.5 to 18.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Death
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2373
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 6.9
Confidence Interval (2-Sided) 95%
-5.5 to 22.8
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion
Hide Description Oxygenation index was calculated as the product of fraction of inspired oxygen (FiO2) and mean airway pressure divided by partial pressure of oxygen dissolved in arterial blood (PaO2) [(FiO2*mean airway pressure)/PaO2] measured in centimeter of water per millimeter of mercury (cmH2O/mmHg). FiO2 is the measure of oxygen concentration that is breathed. Mean airway pressure is defined as an average of the airway pressure throughout the respiratory cycle. PaO2 is the measure of oxygen level dissolved in the arterial blood.
Time Frame Baseline, Hours 6, 12 and 24 after start of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants treated with study treatment. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified rows.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Least Squares Mean (95% Confidence Interval)
Unit of Measure: cmH2O/mmHg
Change at Hour 6 Number Analyzed 29 participants 22 participants
-4.2
(-11.64 to 3.34)
-8.0
(-16.63 to 0.57)
Change at Hour 12 Number Analyzed 28 participants 22 participants
-4.1
(-10.51 to 2.23)
-8.2
(-15.42 to -1.04)
Change at Hour 24 Number Analyzed 18 participants 17 participants
-11.6
(-15.40 to -7.83)
-9.5
(-13.36 to -5.57)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4984
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
-7.5 to 15.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3956
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
-5.5 to 13.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4249
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-7.6 to 3.3
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion
Hide Description Differential oxygenation saturation is a simple way to detect the right-to left shunting at ductus arteriosus using 2 pulse oximeters. It is the difference between pre-ductal and post-ductal sites pulse oxygen saturation (SpO2). Where, pre-duct refers to right upper extremity and post-duct refers to lower limb. Oxygenation saturation is measured as percentage of hemoglobin binding sites occupied by oxygen in the blood.
Time Frame Baseline, Hours 6, 12 and 24 after start of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants treated with study treatment. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified rows.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of hemoglobin
Change at Hour 6 Number Analyzed 26 participants 19 participants
1.5
(-1.79 to 4.80)
0.8
(-3.10 to 4.62)
Change at Hour 12 Number Analyzed 25 participants 19 participants
-1.2
(-7.65 to 5.21)
6.7
(-0.65 to 14.12)
Change at Hour 24 Number Analyzed 19 participants 14 participants
1.2
(-7.15 to 9.49)
9.3
(-0.40 to 19.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7686
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-4.3 to 5.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1112
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -8.0
Confidence Interval (2-Sided) 95%
-17.8 to 1.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2089
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -8.2
Confidence Interval (2-Sided) 95%
-21.2 to 4.8
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24
Hide Description The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen is a ratio between the oxygen level in the arterial blood and the oxygen concentration that is breathed. It helps to determine the degree of any problems with how the lungs transfer oxygen to the blood.
Time Frame Baseline, Hours 6, 12 and 24 after start of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants treated with study treatment. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified rows.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ratio
Change at Hour 6 Number Analyzed 29 participants 23 participants
45.3
(17.21 to 73.37)
8.1
(-23.48 to 39.60)
Change at Hour 12 Number Analyzed 28 participants 24 participants
43.4
(16.76 to 70.13)
16.9
(-11.97 to 45.68)
Change at Hour 24 Number Analyzed 20 participants 17 participants
94.6
(18.52 to 170.69)
14.7
(-67.83 to 97.25)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0829
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 37.2
Confidence Interval (2-Sided) 95%
-5.0 to 79.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1802
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 26.6
Confidence Interval (2-Sided) 95%
-12.7 to 65.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection IV Sildenafil, Placebo
Comments Hour 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1576
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 79.9
Confidence Interval (2-Sided) 95%
-32.5 to 192.2
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite
Hide Description Cmax was obtained for Sildenafil and its major metabolite UK-103,320.
Time Frame Loading dose, Day 1: prior to the start of infusion, 5, 30 minutes after end of loading infusion; Maintenance dose: 48 to 72, 96 to 120 hours during infusion and immediately prior to end of maintenance infusion (up to maximum on Day 14)
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Hide Analysis Population Description
Pharmacokinetic (PK) analysis set included all participants randomized and treated who had at least 1 concentration during whole treatment period.
Arm/Group Title IV Sildenafil
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 25
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter
Loading dose: Sildenafil 52.64  (27.91)
Loading dose: UK-103320 1.04  (1.68)
Maintenance dose: Sildenafil 78.12  (48.63)
Maintenance dose: UK-103320 21.65  (11.57)
10.Secondary Outcome
Title Total Plasma Clearance (CL) of Sildenafil and Its Metabolite
Hide Description CL is volume of the body fluid/ plasma from which the drug or the metabolite is completely removed per unit time. CL was obtained for Sildenafil and its major metabolite UK-103,320.
Time Frame Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants randomized and treated who had at least 1 concentration during whole treatment period.
Arm/Group Title IV Sildenafil
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 25
Mean (Standard Deviation)
Unit of Measure: Liters/hour
Sildenafil 1.78  (0.89)
UK-103,320 5.05  (2.25)
11.Secondary Outcome
Title Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite
Hide Description Vc is the hypothetical volume into which a drug or a metabolite initially distributes upon administration. It was determined by using a population-based analysis, non-linear mixed-effects modeling (NONMEM), version 7.4.0. Vc was calculated for Sildenafil and its major metabolite, UK-103,320.
Time Frame Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants randomized and treated who had at least 1 concentration during whole treatment period.
Arm/Group Title IV Sildenafil
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 25
Mean (Standard Deviation)
Unit of Measure: Liters
Sildenafil 8.76  (1.8)
UK-103,320 15.96  (11.20)
12.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent are events between first infusion of study drug and up to 31 days after end of study drug infusion (up to 45 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Time Frame Baseline up to 31 days after end of study drug infusion (up to 45 days)
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Hide Analysis Population Description
The safety population included all participants treated with study treatment.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
22
  75.9%
19
  63.3%
SAEs
7
  24.1%
2
   6.7%
13.Secondary Outcome
Title Number of Treatment-Emergent Adverse Events (AEs) According to Severity
Hide Description AE: untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent are events between first infusion of study drug and up to 31 days after end of study drug infusion (up to 45 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Severity criteria: mild=did not interfere with subject's usual function; moderate=interfered to some extent with participant's usual function and severe=interfered significantly with participant's usual function. Missing baseline severities were imputed as mild.
Time Frame Baseline up to 31 days after end of study drug infusion (up to 45 days)
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Hide Analysis Population Description
The safety population included all participants treated with study treatment.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 30
Measure Type: Number
Unit of Measure: events
Mild 49 42
Moderate 29 24
Severe 12 17
14.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities
Hide Description Criteria for laboratory values: Hematology: hemoglobin, hematocrit, red blood cell count <0.8*lower limit of normal (LLN), platelets<0.5*LLN, >1.75*upper limit of normal (ULN), white blood cells count <0.6*LLN, >1.5*ULN; Liver function: total and direct bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3.0*ULN, total protein <0.8*LLN, >1.2*ULN; Renal function: blood urea nitrogen, creatinine >1.3*ULN; Electrolytes: sodium <0.95*LLN, >1.05*ULN, potassium, chloride, calcium, bicarbonate (venous) <0.9*LLN, >1.1*ULN.
Time Frame Up to 14 days from initiation of study drug infusion
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants treated with study treatment. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description:
Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
Overall Number of Participants Analyzed 29 28
Measure Type: Count of Participants
Unit of Measure: Participants
27
  93.1%
22
  78.6%
15.Secondary Outcome
Title Part B: Developmental Progress of Participants as Assessed by Bayley Scales of Infant Development and Behavior Questionnaire
Hide Description The results for this outcome measure shall be reported when all participants have completed or discontinued from the 2-year follow-up visit (at the end of 2020).
Time Frame Months 12 and 24 after end of study treatment Part A
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Part B: Visual Status of Participants as Assessed by Eye Examinations of the Anterior and Posterior Segments
Hide Description The results for this outcome measure shall be reported when all participants have completed or discontinued from the 2-year follow-up visit (at the end of 2020).
Time Frame Months 12 and 24 after end of study treatment Part A
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Part B: Audiological Status of Participants as Assessed by Physiological and Behavioral Tests
Hide Description The results for this outcome measure shall be reported when all participants have completed or discontinued from the 2-year follow-up visit (at the end of 2020).
Time Frame Months 12 and 24 after end of study treatment Part A
Outcome Measure Data Not Reported
18.Secondary Outcome
Title Part B: Safety Assessed by Adverse Events and Survival
Hide Description The results for this outcome measure shall be reported when all participants have completed or discontinued from the 2-year follow-up visit (at the end of 2020).
Time Frame Months 12 and 24 after end of study treatment Part A
Outcome Measure Data Not Reported
19.Secondary Outcome
Title Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score
Hide Description The results for this outcome measure shall be reported when all participants have completed or discontinued from the 2-year follow-up visit (at the end of 2020).
Time Frame Months 12 and 24 after end of study treatment Part A
Outcome Measure Data Not Reported
Time Frame Baseline up to 31 days after end of study drug infusion (up to 45 days)
Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another, or a subject may have experienced both serious and non-serious event.
 
Arm/Group Title IV Sildenafil Placebo
Hide Arm/Group Description Part A: Participants received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study. Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.
All-Cause Mortality
IV Sildenafil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2/29 (6.90%)   1/30 (3.33%) 
Hide Serious Adverse Events
IV Sildenafil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   7/29 (24.14%)   2/30 (6.67%) 
Cardiac disorders     
Cardiomyopathy * 1  1/29 (3.45%)  0/30 (0.00%) 
Congenital, familial and genetic disorders     
Pulmonary malformation * 1  0/29 (0.00%)  1/30 (3.33%) 
General disorders     
Drug withdrawal syndrome * 1  1/29 (3.45%)  0/30 (0.00%) 
Infections and infestations     
Urosepsis * 1  0/29 (0.00%)  1/30 (3.33%) 
Metabolism and nutrition disorders     
Hyponatraemia * 1  1/29 (3.45%)  0/30 (0.00%) 
Nervous system disorders     
Myoclonus * 1  1/29 (3.45%)  0/30 (0.00%) 
Seizure * 1  1/29 (3.45%)  0/30 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure * 1  1/29 (3.45%)  0/30 (0.00%) 
Vascular disorders     
Hypertensive crisis * 1  1/29 (3.45%)  0/30 (0.00%) 
Hypotension * 1  1/29 (3.45%)  0/30 (0.00%) 
1
Term from vocabulary, MedDRA v21.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
IV Sildenafil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   20/29 (68.97%)   19/30 (63.33%) 
Blood and lymphatic system disorders     
Anaemia * 1  4/29 (13.79%)  3/30 (10.00%) 
Leukocytosis * 1  2/29 (6.90%)  1/30 (3.33%) 
Thrombocytopenia * 1  0/29 (0.00%)  1/30 (3.33%) 
Cardiac disorders     
Bradycardia * 1  3/29 (10.34%)  1/30 (3.33%) 
Bradycardia neonatal * 1  1/29 (3.45%)  0/30 (0.00%) 
Junctional ectopic tachycardia * 1  0/29 (0.00%)  1/30 (3.33%) 
Myocardial ischaemia * 1  0/29 (0.00%)  1/30 (3.33%) 
Sinus bradycardia * 1  1/29 (3.45%)  0/30 (0.00%) 
Supraventricular tachycardia * 1  1/29 (3.45%)  0/30 (0.00%) 
Congenital, familial and genetic disorders     
Persistent foetal circulation * 1  1/29 (3.45%)  0/30 (0.00%) 
Endocrine disorders     
Hypothyroidism * 1  0/29 (0.00%)  1/30 (3.33%) 
Eye disorders     
Eye oedema * 1  2/29 (6.90%)  0/30 (0.00%) 
Periorbital oedema * 1  1/29 (3.45%)  0/30 (0.00%) 
Pupil fixed * 1  0/29 (0.00%)  1/30 (3.33%) 
Gastrointestinal disorders     
Abdominal distension * 1  1/29 (3.45%)  1/30 (3.33%) 
Diarrhoea * 1  0/29 (0.00%)  1/30 (3.33%) 
Gastric haemorrhage * 1  0/29 (0.00%)  1/30 (3.33%) 
Gastrooesophageal reflux disease * 1  2/29 (6.90%)  1/30 (3.33%) 
Intestinal perforation * 1  0/29 (0.00%)  1/30 (3.33%) 
Vomiting * 1  0/29 (0.00%)  1/30 (3.33%) 
General disorders     
Disease progression * 1  0/29 (0.00%)  1/30 (3.33%) 
Drug withdrawal syndrome * 1  4/29 (13.79%)  0/30 (0.00%) 
Drug withdrawal syndrome neonatal * 1  1/29 (3.45%)  0/30 (0.00%) 
Generalised oedema * 1  0/29 (0.00%)  1/30 (3.33%) 
Infusion site extravasation * 1  1/29 (3.45%)  0/30 (0.00%) 
Malaise * 1  1/29 (3.45%)  0/30 (0.00%) 
Oedema * 1  1/29 (3.45%)  3/30 (10.00%) 
Secretion discharge * 1  0/29 (0.00%)  1/30 (3.33%) 
Withdrawal syndrome * 1  0/29 (0.00%)  1/30 (3.33%) 
Hepatobiliary disorders     
Cholestasis * 1  2/29 (6.90%)  1/30 (3.33%) 
Hyperbilirubinaemia * 1  1/29 (3.45%)  3/30 (10.00%) 
Jaundice cholestatic * 1  0/29 (0.00%)  1/30 (3.33%) 
Infections and infestations     
Conjunctivitis * 1  0/29 (0.00%)  1/30 (3.33%) 
Lung infection * 1  0/29 (0.00%)  1/30 (3.33%) 
Nosocomial infection * 1  0/29 (0.00%)  1/30 (3.33%) 
Pneumonia * 1  0/29 (0.00%)  1/30 (3.33%) 
Sepsis * 1  0/29 (0.00%)  2/30 (6.67%) 
Tracheitis * 1  1/29 (3.45%)  0/30 (0.00%) 
Injury, poisoning and procedural complications     
Procedural hypertension * 1  0/29 (0.00%)  1/30 (3.33%) 
Procedural hypotension * 1  0/29 (0.00%)  1/30 (3.33%) 
Transfusion reaction * 1  0/29 (0.00%)  1/30 (3.33%) 
Underdose * 1  0/29 (0.00%)  1/30 (3.33%) 
Investigations     
Alanine aminotransferase increased * 1  0/29 (0.00%)  1/30 (3.33%) 
Blood albumin decreased * 1  1/29 (3.45%)  0/30 (0.00%) 
Blood calcium decreased * 1  0/29 (0.00%)  1/30 (3.33%) 
Blood magnesium decreased * 1  0/29 (0.00%)  1/30 (3.33%) 
Blood methaemoglobin present * 1  1/29 (3.45%)  0/30 (0.00%) 
Blood urea increased * 1  0/29 (0.00%)  1/30 (3.33%) 
C-reactive protein increased * 1  0/29 (0.00%)  3/30 (10.00%) 
Haematocrit decreased * 1  1/29 (3.45%)  0/30 (0.00%) 
Hepatic enzyme increased * 1  1/29 (3.45%)  0/30 (0.00%) 
Oxygen saturation decreased * 1  1/29 (3.45%)  0/30 (0.00%) 
PCO2 decreased * 1  1/29 (3.45%)  0/30 (0.00%) 
Platelet count decreased * 1  0/29 (0.00%)  1/30 (3.33%) 
Staphylococcus test positive * 1  0/29 (0.00%)  1/30 (3.33%) 
Thyroid function test abnormal * 1  0/29 (0.00%)  1/30 (3.33%) 
Metabolism and nutrition disorders     
Acidosis * 1  0/29 (0.00%)  1/30 (3.33%) 
Alkalosis hypochloraemic * 1  1/29 (3.45%)  0/30 (0.00%) 
Feeding intolerance * 1  0/29 (0.00%)  1/30 (3.33%) 
Fluid overload * 1  2/29 (6.90%)  0/30 (0.00%) 
Fluid retention * 1  1/29 (3.45%)  1/30 (3.33%) 
Hyperchloraemia * 1  0/29 (0.00%)  1/30 (3.33%) 
Hyperkalaemia * 1  0/29 (0.00%)  1/30 (3.33%) 
Hypernatraemia * 1  0/29 (0.00%)  1/30 (3.33%) 
Hypoalbuminaemia * 1  1/29 (3.45%)  1/30 (3.33%) 
Hypocalcaemia * 1  1/29 (3.45%)  0/30 (0.00%) 
Hypochloraemia * 1  1/29 (3.45%)  0/30 (0.00%) 
Hypoglycaemia * 1  0/29 (0.00%)  1/30 (3.33%) 
Hypokalaemia * 1  7/29 (24.14%)  0/30 (0.00%) 
Hypoproteinaemia * 1  1/29 (3.45%)  0/30 (0.00%) 
Metabolic acidosis * 1  1/29 (3.45%)  0/30 (0.00%) 
Nervous system disorders     
Brain injury * 1  1/29 (3.45%)  0/30 (0.00%) 
Cerebral ischaemia * 1  1/29 (3.45%)  0/30 (0.00%) 
Hypertonia * 1  0/29 (0.00%)  1/30 (3.33%) 
Motor dysfunction * 1  1/29 (3.45%)  0/30 (0.00%) 
Seizure * 1  2/29 (6.90%)  1/30 (3.33%) 
Vocal cord paralysis * 1  1/29 (3.45%)  0/30 (0.00%) 
Psychiatric disorders     
Selective eating disorder * 1  0/29 (0.00%)  1/30 (3.33%) 
Renal and urinary disorders     
Oliguria * 1  1/29 (3.45%)  0/30 (0.00%) 
Renal failure * 1  0/29 (0.00%)  1/30 (3.33%) 
Reproductive system and breast disorders     
Oedema genital * 1  1/29 (3.45%)  0/30 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Choking * 1  1/29 (3.45%)  0/30 (0.00%) 
Hiccups * 1  1/29 (3.45%)  0/30 (0.00%) 
Hypoxia * 1  1/29 (3.45%)  0/30 (0.00%) 
Lung disorder * 1  0/29 (0.00%)  1/30 (3.33%) 
Neonatal asphyxia * 1  1/29 (3.45%)  0/30 (0.00%) 
Pneumothorax * 1  2/29 (6.90%)  4/30 (13.33%) 
Productive cough * 1  0/29 (0.00%)  1/30 (3.33%) 
Pulmonary air leakage * 1  0/29 (0.00%)  1/30 (3.33%) 
Pulmonary interstitial emphysema syndrome * 1  0/29 (0.00%)  1/30 (3.33%) 
Pulmonary oedema * 1  0/29 (0.00%)  1/30 (3.33%) 
Respiratory distress * 1  0/29 (0.00%)  1/30 (3.33%) 
Respiratory failure * 1  0/29 (0.00%)  2/30 (6.67%) 
Respiratory tract oedema * 1  1/29 (3.45%)  0/30 (0.00%) 
Rhinorrhoea * 1  0/29 (0.00%)  1/30 (3.33%) 
Stridor * 1  1/29 (3.45%)  0/30 (0.00%) 
Tachypnoea * 1  1/29 (3.45%)  0/30 (0.00%) 
Atelectasis * 1  2/29 (6.90%)  2/30 (6.67%) 
Skin and subcutaneous tissue disorders     
Dermatitis diaper * 1  0/29 (0.00%)  2/30 (6.67%) 
Rash * 1  1/29 (3.45%)  0/30 (0.00%) 
Rash erythematous * 1  0/29 (0.00%)  1/30 (3.33%) 
Skin irritation * 1  1/29 (3.45%)  0/30 (0.00%) 
Vascular disorders     
Haemodynamic instability * 1  1/29 (3.45%)  0/30 (0.00%) 
Hypertension * 1  2/29 (6.90%)  0/30 (0.00%) 
Hypotension * 1  7/29 (24.14%)  3/30 (10.00%) 
1
Term from vocabulary, MedDRA v21.1
*
Indicates events were collected by non-systematic assessment
The results for Part B outcome measures shall be reported once all participants have completed or discontinued from the 2-year follow-up visit (at the end of 2020).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 8007181021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01720524    
Other Study ID Numbers: A1481316
2012-002619-24 ( EudraCT Number )
First Submitted: September 17, 2012
First Posted: November 2, 2012
Results First Submitted: October 16, 2019
Results First Posted: March 25, 2020
Last Update Posted: November 27, 2020