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Inositol to Reduce Retinopathy of Prematurity (INS-3)

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ClinicalTrials.gov Identifier: NCT01954082
Recruitment Status : Terminated (Study terminated due to safety concerns; participant follow up will continue until March 2018)
First Posted : October 1, 2013
Results First Posted : September 26, 2018
Last Update Posted : September 26, 2018
Sponsor:
Collaborators:
National Eye Institute (NEI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
NICHD Neonatal Research Network

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Retinopathy of Prematurity (ROP)
Interventions Drug: myo-Inositol 5% Injection
Drug: Placebo
Enrollment 638
Recruitment Details From April 2014 to September 2015, infants born before 28 weeks gestation and surviving >12 hours were screened when admitted to one of the 18 NICHD NRN Centers (approximately 44 sites) in the United States and enrolled in the study if they met the eligibility criteria and consent was obtained before 72 hours postnatal age.
Pre-assignment Details  
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally. The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
Period Title: Overall Study
Started 317 321
Treated 313 [1] 319 [2]
Completed 249 [3] 264 [4]
Not Completed 68 57
Reason Not Completed
Study Suspension             42             36
Adverse Event             10             4
Intolerance             0             1
Non-compliance             6             4
Physician Decision             2             0
Parent Decision             1             0
Withdrawal by Subject             0             1
Discontinued Early Prior to Transfer             3             2
Redirection of Care             0             2
Miscalculation of Final Dose Day             0             3
Comfort Care             0             1
Infant Moved             0             1
Randomized not Treated             4             2
[1]
The 4 participants who were not treated either died (3) or withdrew before treatment start (1).
[2]
The 2 participants who were not treated died before treatment start.
[3]
There were 22 infants that received more doses than intended per protocol.
[4]
There were 27 infants that received more doses than intended per protocol.
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose) Total
Hide Arm/Group Description Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally. The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol. Total of all reporting groups
Overall Number of Baseline Participants 317 321 638
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 317 participants 321 participants 638 participants
25.64  (1.42) 25.72  (1.34) 25.68  (1.38)
Age, Continuous  
Median (Full Range)
Unit of measure:  Weeks
Number Analyzed 317 participants 321 participants 638 participants
25.9
(22.0 to 27.9)
25.9
(22.7 to 27.9)
25.9
(22.0 to 27.9)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Gestational Age Number Analyzed 317 participants 321 participants 638 participants
<26 weeks
169
  53.3%
170
  53.0%
339
  53.1%
>=26 weeks
148
  46.7%
151
  47.0%
299
  46.9%
Age, Customized   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
AGE AT START OF STUDY THERAPY Number Analyzed 313 participants 319 participants 632 participants
2.8  (0.8) 2.8  (0.8) 2.8  (0.8)
[1]
Measure Analysis Population Description: Age at start of study therapy is only available for infants who started treatment (313 Inositol and 319 Placebo).
Age, Customized   [1] 
Median (Full Range)
Unit of measure:  Days
AGE AT START OF STUDY THERAPY Number Analyzed 313 participants 319 participants 632 participants
3
(1 to 5)
3
(1 to 7)
3
(1 to 7)
[1]
Measure Analysis Population Description: Age at start of study therapy is only available for infants who started treatment (313 Inositol and 319 Placebo).
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 317 participants 321 participants 638 participants
Female
159
  50.2%
158
  49.2%
317
  49.7%
Male
158
  49.8%
163
  50.8%
321
  50.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race/Ethnicity Number Analyzed 317 participants 321 participants 638 participants
Asian
11
   3.5%
6
   1.9%
17
   2.7%
Black Not Hispanic or Latino
119
  37.5%
113
  35.2%
232
  36.4%
Hispanic or Latino
38
  12.0%
45
  14.0%
83
  13.0%
Other
3
   0.9%
11
   3.4%
14
   2.2%
White Not Hispanic or Latino
133
  42.0%
132
  41.1%
265
  41.5%
Unknown/Not Reported
13
   4.1%
14
   4.4%
27
   4.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 317 participants 321 participants 638 participants
317
 100.0%
321
 100.0%
638
 100.0%
BIRTH WEIGHT  
Mean (Standard Deviation)
Unit of measure:  Grams
Number Analyzed 317 participants 321 participants 638 participants
776.1  (195) 784.6  (198.2) 780.4  (196.5)
BIRTH WEIGHT  
Median (Full Range)
Unit of measure:  Grams
Number Analyzed 317 participants 321 participants 638 participants
740
(394 to 1390)
765
(300 to 1589)
750
(300 to 1589)
ANTENATAL STEROIDS  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 317 participants 321 participants 638 participants
No
36
  11.4%
37
  11.5%
73
  11.4%
Yes
281
  88.6%
283
  88.2%
564
  88.4%
Unknown/Not Reported
0
   0.0%
1
   0.3%
1
   0.2%
EARLY ONSET SEPSIS  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 317 participants 321 participants 638 participants
No
310
  97.8%
312
  97.2%
622
  97.5%
Yes
7
   2.2%
9
   2.8%
16
   2.5%
APGAR-5 MINUTE  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 317 participants 321 participants 638 participants
Test Result Available
313
  98.7%
316
  98.4%
629
  98.6%
Test Result Not Available
4
   1.3%
5
   1.6%
9
   1.4%
APGAR-5 MINUTE   [1] 
Median (Full Range)
Unit of measure:  Units on a Scale
Number Analyzed 317 participants 321 participants 638 participants
7
(0 to 9)
6
(0 to 9)
6
(0 to 9)
[1]
Measure Description: 10-point, ordinal scale specifying infant's overall health 5 minutes after birth from 1 (needs immediate medical help) to 10 (in optimal health).
1.Primary Outcome
Title Number of Participants With Unfavorable Outcome, Defined as Severe Retinopathy of Prematurity (ROP) or Death Prior to Reaching Acute/Final ROP Status
Hide Description Death is defined as from any cause before Acute/Final ROP status is determined. ROP was identified by routine ophthalmologic examinations beginning at the latter of 31 weeks PMA or 4-6 weeks chronologic age. The favorable ROP endpoint requires that no ROP, or only mild ROP has occurred in both eyes and the eyes have matured beyond the risk of developing Type 1 ROP (severity meeting criteria for surgical intervention). The unfavorable ROP endpoint requires that one or both eyes reach Type 1 ROP. When ROP did not resolve by the time of discharge, participants were followed as outpatients until reaching an ROP endpoint, up to 55 weeks PMA. Since incomplete follow up is more likely among participants with mild or no ROP than for those with aggressive ROP, an independent adjudication process assigned an ROP endpoint of ‘most likely never had Type 1 ROP’, or ‘most likely developed Type 1 ROP’ based on clinical and ROP data review to reduce possible missing data bias.
Time Frame by 55 weeks PMA
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on an intention to treat basis, including adjudicated ROP endpoints. Individuals for whom adjudicated ROP endpoints could not be obtained were treated as missing completely at random, and excluded from the primary analyses (4 Inositol and 1 Placebo).
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description:
Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally.
The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
Overall Number of Participants Analyzed 313 320
Measure Type: Count of Participants
Unit of Measure: Participants
91
  29.1%
66
  20.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 5% Glucose(Dextrose)
Comments The null hypothesis is there is no treatment effect on the development of severe ROP and mortality.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0095
Comments A-priori threshold for statistical significance at 0.05 was specified.
Method Robust Poisson
Comments Model adjusted for strata defined by center and gestational age.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
1.08 to 1.83
Estimation Comments In the risk ratio, the numerator represents the Inositol arm and the denominator represents the placebo arm. (RR>1 implies that the risk of mortality and/or severe ROP is greater in the Inositol group compared to the Placebo group).
2.Secondary Outcome
Title Number of Participants With Bronchopulmonary Dysplasia (BPD)
Hide Description BPD is defined as supplemental oxygen required to maintain an oxygenation saturation of >90% at 36 weeks postmenstrual age (PMA) (NICHD physiologic definition).
Time Frame 36 weeks PMA
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on an intention to treat basis. Individuals for whom BPD outcome could not be obtained were treated as missing completely at random, and excluded from the analyses (45 Inositol and 33 Placebo).
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description:
Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally.
The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
Overall Number of Participants Analyzed 272 288
Measure Type: Count of Participants
Unit of Measure: Participants
159
  58.5%
165
  57.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 5% Glucose(Dextrose)
Comments The null hypothesis is there is no treatment effect on the incidence of BPD.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6599
Comments A-priori threshold for statistical significance at 0.05 was specified.
Method Robust Poisson regression
Comments Model adjusted for strata defined by center and gestational age.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.91 to 1.16
Estimation Comments In the risk ratio, the numerator represents the Inositol arm and the denominator represents the placebo arm. (RR>1 implies that the risk of BPD is greater in the Inositol group compared to the Placebo group).
3.Secondary Outcome
Title Number of Participants With Bronchopulmonary Dysplasia (BPD) or Death From BPD
Hide Description BPD is defined as supplemental oxygen required to maintain an oxygenation saturation of >90% at 36 weeks PMA (NICHD physiologic definition). Death from BPD prior to 37 weeks postmenstrual age (PMA) is defined when the cause of death is certified by the Center PI as BPD being the primary cause, or a significant co-contributing cause of death.
Time Frame prior to 37 weeks PMA
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on an intention to treat basis. Individuals who died prior to 37 weeks PMA for whom the cause(s) of death are unknown or individuals for whom BPD outcome could not be obtained were treated as missing completely at random, and excluded from the analyses (1 Inositol and 5 Placebo).
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description:
Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally.
The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
Overall Number of Participants Analyzed 316 316
Measure Type: Count of Participants
Unit of Measure: Participants
203
  64.2%
195
  61.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 5% Glucose(Dextrose)
Comments The null hypothesis is there is no treatment effect on the incidence of BPD or on mortality due to BDP.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3883
Comments A-priori threshold for statistical significance at 0.05 was specified.
Method Robust Poisson regression
Comments Model adjusted for strata defined by center and gestational age.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.94 to 1.17
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With All Cause Death Before Retinopathy of Prematurity (ROP) Endpoint
Hide Description Defined as death from any cause following randomization through primary study follow-up (up to 55 weeks postmenstrual age (PMA))
Time Frame by 55 weeks PMA age
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on an intention to treat basis.
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description:
Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally.
The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
Overall Number of Participants Analyzed 317 321
Measure Type: Count of Participants
Unit of Measure: Participants
50
  15.8%
33
  10.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 5% Glucose(Dextrose)
Comments The null hypothesis is there is no treatment effect on survival to ROP endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0306
Comments A-priori threshold for statistical significance at 0.05 was specified.
Method Robust Poisson regression
Comments Model adjusted for strata defined by center and gestational age.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.53
Confidence Interval (2-Sided) 95%
1.03 to 2.25
Estimation Comments In the risk ratio, the numerator represents the Inositol arm and the denominator represents the placebo arm. (RR>1 implies that the risk of mortality prior to ROP endpoint is greater in the Inositol group compared to the Placebo group).
5.Secondary Outcome
Title Number of Participants With Any Retinopathy of Prematurity (ROP)
Hide Description ROP was identified by routine ophthalmologic examinations beginning at the latter of 31 weeks PMA or 4-6 weeks chronologic age. Any ROP is defined as ROP of any severity that is observed on at least 2 independent examinations in either eye through the time that Acute/Final ROP status is reached (up to 55 weeks postmenstrual age (PMA)).
Time Frame by 55 weeks PMA
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on an intention to treat basis. Individuals for whom ROP status could not be defined were treated as missing completely at random, and excluded from the analyses (50 Inositol and 35 Placebo).
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description:
Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally.
The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
Overall Number of Participants Analyzed 267 286
Measure Type: Count of Participants
Unit of Measure: Participants
171
  64.0%
183
  64.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 5% Glucose(Dextrose)
Comments The null hypothesis is there is no treatment effect on the incidence of ROP
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7464
Comments A-priori threshold for statistical significance at 0.05 was specified.
Method Robust Poisson regression
Comments Model adjusted for strata defined by center and gestational age.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.91 to 1.14
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Type 2 or More Severe Retinopathy of Prematurity (ROP)
Hide Description Defined as one or both eyes reaching Type 2 ROP (ETROP 2003) or the more severe Type 1 ROP (as defined previously) through the time that Acute/Final ROP status is reached (up to 55 weeks postmenstrual age (PMA)). Type 2 ROP is defined as (ETROP 2003): Stage 3 ROP without Plus Disease (i.e. Zone II) or Stage 1 or 2 ROP without Plus Disease (i.e. Zone I).
Time Frame by 55 weeks PMA
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on an intention to treat basis. Individuals for whom ROP status and/or type could not be defined were treated as missing completely at random, and excluded from the analyses (54 Inositol and 36 Placebo).
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description:
Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally.
The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
Overall Number of Participants Analyzed 263 285
Measure Type: Count of Participants
Unit of Measure: Participants
125
  47.5%
142
  49.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 5% Glucose(Dextrose)
Comments The null hypothesis is there is no treatment effect on the incidence of Type 2 ROP or more severe ROP.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7598
Comments A-priori threshold for statistical significance at 0.05 was specified.
Method Robust Poisson regression
Comments Model adjusted for strata defined by center and gestational age.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.83 to 1.14
Estimation Comments In the risk ratio, the numerator represents the Inositol arm and the denominator represents the placebo arm. (RR>1 implies that the risk of Type 2 ROP or more severe ROP is greater in the Inositol group compared to the Placebo group).
7.Secondary Outcome
Title Number of Participants With Severe Intraventricular Hemorrhage (IVH)
Hide Description Severe IVH is defined as IVH Grades 3 or 4 on either side of the brain. The evaluation for IVH occurs early (within 28 days from birth) via a cranial sonogram and is classified as described by Papile.
Time Frame by 28 days PMA
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on an intention to treat basis. Individuals for whom severe IVH status could not be defined were treated as missing completely at random, and excluded from the analyses (6 Inositol and 4 Placebo).
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description:
Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally.
The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
Overall Number of Participants Analyzed 311 317
Measure Type: Count of Participants
Unit of Measure: Participants
51
  16.4%
50
  15.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 5% Glucose(Dextrose)
Comments The null hypothesis is there is no treatment effect on the incidence severe IVH.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8133
Comments A-priori threshold for statistical significance at 0.05 was specified.
Method Robust Poisson regression
Comments Model adjusted for strata defined by center and gestational age.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.74 to 1.48
Estimation Comments In the risk ratio, the numerator represents the Inositol arm and the denominator represents the placebo arm. (RR>1 implies that the risk of severe IVH is greater in the Inositol group compared to the Placebo group).
8.Other Pre-specified Outcome
Title The Occurrence of Adverse Events and Serious Adverse Events
Hide Description [Not Specified]
Time Frame 7 days post study drug discontinuation
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title Necrotizing Enterocolitis (NEC)
Hide Description Stage II or worse, whether treated (medically or surgically) and if the infant survived (modified Bell's classification [Walsh 1986]).
Time Frame NRN infant status, i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Isolated Gastrointestinal Perforation
Hide Description judged not to be due to NEC
Time Frame NRN infant status, i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title Late Onset Sepsis
Hide Description culture positive septicemia/bacteremia (≥72 hours of age) treated with antibiotics for ≥ 5 days or died before treatment was completed.
Time Frame NRN infant status, i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Outcome Measure Data Not Reported
12.Other Pre-specified Outcome
Title Patent Ductus Arteriosus (PDA)
Hide Description Occurrence of clinically significant patent ductus arteriosus (PDA), and if received intervention with prostaglandin inhibitors, and/or surgery.
Time Frame NRN infant status, i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Outcome Measure Data Not Reported
13.Other Pre-specified Outcome
Title Seizures
Hide Description Seizures treated with an anticonvulsant for >72 hours
Time Frame NRN infant status, i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Outcome Measure Data Not Reported
14.Other Pre-specified Outcome
Title Total Days on Parenteral Nutrition
Hide Description Total days on parenteral nutrition (including amino acids and/or lipids)
Time Frame NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Outcome Measure Data Not Reported
15.Other Pre-specified Outcome
Title Days on Oxygen, Days on Ventilator
Hide Description [Not Specified]
Time Frame NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Outcome Measure Data Not Reported
16.Other Pre-specified Outcome
Title Hearing Loss
Hide Description Hearing loss as defined as never passing a hearing screening in one or both ears
Time Frame NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Outcome Measure Data Not Reported
17.Other Pre-specified Outcome
Title Neurodevelopment
Hide Description Neurodevelopment at 22-26 months corrected age (i.e., 22-26 months past due date) using the Bayley Scales of Infant Development III.
Time Frame 22-26 months corrected age
Outcome Measure Data Not Reported
18.Other Pre-specified Outcome
Title Vision Loss
Hide Description Vision loss as diagnosed by an ophthalmologist as legally blind, and subdivided into “ophthalmic origin”, or “not ophthalmic origin” (i.e., cortical blindness is non-ophthalmic in origin and indicates that there is no retinal detachment or other abnormal fundus or ocular finding, except optic atrophy. Such cases will be considered central [neurologic] in origin.)
Time Frame 22-26 Months Corrected Age
Outcome Measure Data Not Reported
19.Other Pre-specified Outcome
Title Hearing Loss
Hide Description Hearing loss requiring that hearing aids be prescribed.
Time Frame 22-26 Months Corrected Age
Outcome Measure Data Not Reported
20.Other Pre-specified Outcome
Title Cerebral Palsy
Hide Description Cerebral palsy by severity category (absent/mild/moderate/severe).
Time Frame 22-26 Months Corrected Age
Outcome Measure Data Not Reported
21.Other Pre-specified Outcome
Title Overall Health Status
Hide Description Overall health status per recall from the parent/guardian (including survival, re-hospitalizations, surgeries, ongoing medications, and chronic illnesses).
Time Frame 22-26 Months Corrected Age
Outcome Measure Data Not Reported
Time Frame Adverse events will be recorded from treatment initiation until 7 days after the last dose of study drug, up to the earliest of 34 weeks post-menstrual age (PMA), 10 weeks chronologic age (CA), or discharge.
Adverse Event Reporting Description The at-risk population for all-cause mortality is the intent-to-treat (ITT) population which consists of all randomized participants (317 Inositol 321 Placebo). The at-risk population for serious adverse events and/or other (not including serious) adverse events is the safety-population which consists of all individuals who started treatment (313 Inositol 319 Placebo).
 
Arm/Group Title Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Hide Arm/Group Description Inositol (i.e myo-Inositol) 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. The medication is administered twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose) begining within 12-72 hours of birth and continuing until the earliest of 34 weeks postmenstrual age (PMA), 10 weeks chronologic age, or the time of discharge. The doses are administered intravenously (IV) using syringe pump over 15-30 minutes until enteral feeds reach 120ml/kg/day (or sooner if the infant is no longer receiving IV fluids), at which time the same dose and formulation will be administered enterally. The placebo is 5% dextrose (5% glucose) in sterile water (D5W pyrogen and preservative free) United States Pharmacopoeia (USP) for IV infusion. The placebo is administered in the same dose (80 mg glucose/kg/day divided in 2 doses administered every 12 hours) and dispensed in the same manner (intravenously or enterally) as the inositol.
All-Cause Mortality
Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Affected / at Risk (%) Affected / at Risk (%)
Total   50/317 (15.77%)      33/321 (10.28%)    
Show Serious Adverse Events Hide Serious Adverse Events
Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   113/313 (36.10%)      105/319 (32.92%)    
Blood and lymphatic system disorders     
ANEMIA   14/313 (4.47%)  15 10/319 (3.13%)  11
HYPERBILIRUBINEMIA   0/313 (0.00%)  0 1/319 (0.31%)  1
NEUTROPENIA   1/313 (0.32%)  1 5/319 (1.57%)  5
THROMBOCYTOPENIA   9/313 (2.88%)  9 9/319 (2.82%)  9
THROMBOCYTOSIS   1/313 (0.32%)  1 0/319 (0.00%)  0
COAGULOPATHY   1/313 (0.32%)  1 1/319 (0.31%)  1
LEUKOCYTOSIS   1/313 (0.32%)  1 0/319 (0.00%)  0
Cardiac disorders     
BRADYCARDIA   0/313 (0.00%)  0 2/319 (0.63%)  2
CONGESTIVE HEART FAILURE   0/313 (0.00%)  0 1/319 (0.31%)  1
HYPERTENSION   0/313 (0.00%)  0 2/319 (0.63%)  2
PDA   8/313 (2.56%)  8 13/319 (4.08%)  13
POOR PERFUSION OR HYPOTENSION   23/313 (7.35%)  24 14/319 (4.39%)  16
CARDIOPULMONARY ARREST   1/313 (0.32%)  1 0/319 (0.00%)  0
PULMONARY VALVE STENOSIS   1/313 (0.32%)  1 0/319 (0.00%)  0
Endocrine disorders     
ADRENAL INSUFFICENCY   1/313 (0.32%)  1 1/319 (0.31%)  1
Gastrointestinal disorders     
CHOLESTASIS   9/313 (2.88%)  9 3/319 (0.94%)  3
DELAYED GASTRIC EMPTYING   1/313 (0.32%)  1 1/319 (0.31%)  1
ELEVATED LIVER ENZYMES   3/313 (0.96%)  3 0/319 (0.00%)  0
EMESIS   0/313 (0.00%)  0 1/319 (0.31%)  1
NEC   19/313 (6.07%)  20 14/319 (4.39%)  16
SPONTANEOUS INTESTINAL PERFORATION, WITHOUT NEC   15/313 (4.79%)  17 20/319 (6.27%)  24
ESPHOGEAL PERFORATION   3/313 (0.96%)  3 1/319 (0.31%)  1
ILEUS   1/313 (0.32%)  1 1/319 (0.31%)  1
MECONIUM PLUG SYNDROME   1/313 (0.32%)  1 0/319 (0.00%)  0
Hepatobiliary disorders     
HEPATIC FAILURE   0/313 (0.00%)  0 2/319 (0.63%)  2
Infections and infestations     
SYSTEMIC INFECTION   50/313 (15.97%)  55 34/319 (10.66%)  39
Metabolism and nutrition disorders     
HYPERGLYCEMIA   6/313 (1.92%)  6 5/319 (1.57%)  6
HYPOGLYCEMIA   1/313 (0.32%)  1 0/319 (0.00%)  0
ACIDOSIS   2/313 (0.64%)  2 3/319 (0.94%)  3
HYPERCALCEMIA   1/313 (0.32%)  1 0/319 (0.00%)  0
HYPONATREMIA   1/313 (0.32%)  1 1/319 (0.31%)  1
HYPERNATREMIA   1/313 (0.32%)  1 0/319 (0.00%)  0
Musculoskeletal and connective tissue disorders     
COMPARTMENT SYNDROME   1/313 (0.32%)  1 0/319 (0.00%)  0
Nervous system disorders     
IVH   31/313 (9.90%)  33 30/319 (9.40%)  32
SEIZURES   1/313 (0.32%)  1 3/319 (0.94%)  3
Renal and urinary disorders     
DIURESIS   1/313 (0.32%)  1 0/319 (0.00%)  0
ELEVATED CREATININE   3/313 (0.96%)  3 0/319 (0.00%)  0
HYPERKALEMIA   4/313 (1.28%)  4 4/319 (1.25%)  4
HEMATURIA   1/313 (0.32%)  1 1/319 (0.31%)  1
OLIGURIA   11/313 (3.51%)  13 7/319 (2.19%)  8
PROTEINURIA   1/313 (0.32%)  1 0/319 (0.00%)  0
RENAL FAILURE   4/313 (1.28%)  4 2/319 (0.63%)  2
Respiratory, thoracic and mediastinal disorders     
PULMONARY AIR LEAK   11/313 (3.51%)  12 9/319 (2.82%)  10
PULMONARY HEMORRHAGE   5/313 (1.60%)  5 16/319 (5.02%)  17
PULMONARY HYPERTENSION   2/313 (0.64%)  2 2/319 (0.63%)  2
RESPIRATORY DETERIORATION   10/313 (3.19%)  10 11/319 (3.45%)  11
HYPOXIC RESPIRATORY FAILURE   1/313 (0.32%)  1 0/319 (0.00%)  0
Skin and subcutaneous tissue disorders     
SUPERFICIAL INFECTION   0/313 (0.00%)  0 1/319 (0.31%)  1
SKIN BREAKDOWN   0/313 (0.00%)  0 2/319 (0.63%)  2
SKIN CELLULITIS   0/313 (0.00%)  0 1/319 (0.31%)  1
Vascular disorders     
THROMBOSIS   1/313 (0.32%)  1 0/319 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Myo-Inositol 5% Injection 5% Glucose(Dextrose)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   291/313 (92.97%)      298/319 (93.42%)    
Blood and lymphatic system disorders     
ANEMIA   185/313 (59.11%)  336 202/319 (63.32%)  379
HYPERBILIRUBINEMIA   67/313 (21.41%)  69 56/319 (17.55%)  63
NEUTROPENIA   30/313 (9.58%)  31 30/319 (9.40%)  36
THROMBOCYTOPENIA   31/313 (9.90%)  40 26/319 (8.15%)  37
THROMBOCYTOSIS   95/313 (30.35%)  108 96/319 (30.09%)  119
OTHER  [1]  0/313 (0.00%)  0 1/319 (0.31%)  1
Cardiac disorders     
CONGESTIVE HEART FAILURE   20/313 (6.39%)  20 19/319 (5.96%)  22
HYPERTENSION   23/313 (7.35%)  32 23/319 (7.21%)  36
PDA   88/313 (28.12%)  89 87/319 (27.27%)  87
POOR PERFUSION OR HYPOTENSION   36/313 (11.50%)  45 30/319 (9.40%)  40
TACHYCARDIA   11/313 (3.51%)  14 9/319 (2.82%)  16
OTHER  [2]  0/313 (0.00%)  0 2/319 (0.63%)  2
Endocrine disorders     
ADRENAL INSUFFICIENCY   0/313 (0.00%)  0 4/319 (1.25%)  4
Gastrointestinal disorders     
CHOLEOSTASIS   36/313 (11.50%)  36 26/319 (8.15%)  26
DELAYED GASTRIC EMPTYING   52/313 (16.61%)  76 46/319 (14.42%)  95
DIARRHEA   4/313 (1.28%)  4 2/319 (0.63%)  2
ELEVATED LIVER ENZYMERS   18/313 (5.75%)  20 16/319 (5.02%)  17
EMESIS   2/313 (0.64%)  2 4/319 (1.25%)  4
NEC   16/313 (5.11%)  16 14/319 (4.39%)  14
SPONTANEOUS INTESTINAL PERFORATION WITHOUT NEC   2/313 (0.64%)  2 2/319 (0.63%)  2
ABDOMINAL DISTENTION *  0/313 (0.00%)  1/319 (0.31%)  1
BLOODY STOOL *  1/313 (0.32%)  1 1/319 (0.31%)  1
BOWEL DYSFUNCTION *  0/313 (0.00%)  0 1/319 (0.31%)  1
ESOPHOGEAL PERFORATION   1/313 (0.32%)  1 0/319 (0.00%)  0
FEEDING INTOLERANCE *  2/313 (0.64%)  3 2/319 (0.63%)  2
GASTRITIS   1/313 (0.32%)  1 1/319 (0.31%)  1
GASTROINTESTINAL FISTULA   0/313 (0.00%)  0 2/319 (0.63%)  2
ILEUS   0/313 (0.00%)  0 1/319 (0.31%)  1
STRICTURES REQUIRING SURGERY   1/313 (0.32%)  1 0/319 (0.00%)  0
GRANULATION TISSUE PROLAPSE (PENROSE DRAIN SITE)   1/313 (0.32%)  1 0/319 (0.00%)  0
Infections and infestations     
LOCAL INFECTION   10/313 (3.19%)  10 8/319 (2.51%)  9
SUPERFICIAL INFECTION   10/313 (3.19%)  11 18/319 (5.64%)  18
SYSTEMIC INFECTION   76/313 (24.28%)  98 84/319 (26.33%)  102
URINARY TRACT INFECTION   0/313 (0.00%)  0 1/319 (0.31%)  1
Metabolism and nutrition disorders     
HYPERGLYCEMIA   78/313 (24.92%)  97 67/319 (21.00%)  88
HYPOGLYCEMIA   7/313 (2.24%)  10 10/319 (3.13%)  10
HYPOTHERMIA   3/313 (0.96%)  3 0/319 (0.00%)  0
ACIDOSIS   1/313 (0.32%)  1 5/319 (1.57%)  5
ELECTROLYTE IMBALANCE   0/313 (0.00%)  0 4/319 (1.25%)  4
FAILURE TO THRIVE *  0/313 (0.00%)  0 1/319 (0.31%)  1
HYPERTHYROIDISM   0/313 (0.00%)  0 1/319 (0.31%)  1
HYPOTHYROIDISM   0/313 (0.00%)  0 3/319 (0.94%)  3
ELEVATED 17-OH PROGESTERONE   0/313 (0.00%)  0 1/319 (0.31%)  1
RICKETS   0/313 (0.00%)  0 2/319 (0.63%)  2
HYPOCALCEMIA   1/313 (0.32%)  1 2/319 (0.63%)  2
HYPOPHOSPHATEMIA   1/313 (0.32%)  1 1/319 (0.31%)  1
HYPONATREMIA   7/313 (2.24%)  7 5/319 (1.57%)  5
HYPERNATREMIA   0/313 (0.00%)  0 1/319 (0.31%)  1
HYPERTRIGLYCERIDEMIA   0/313 (0.00%)  0 3/319 (0.94%)  3
Musculoskeletal and connective tissue disorders     
OSTEOPENIA   4/313 (1.28%)  4 6/319 (1.88%)  6
OSTEOPOROSIS   0/313 (0.00%)  0 1/319 (0.31%)  1
Nervous system disorders     
ABNORMAL MOVEMENTS   0/313 (0.00%)  0 1/319 (0.31%)  1
IVH   36/313 (11.50%)  36 33/319 (10.34%)  33
SEIZURES   8/313 (2.56%)  8 5/319 (1.57%)  5
STATE OF ALERTNESS   3/313 (0.96%)  5 3/319 (0.94%)  3
INTRACRANIAL HEMORRHAGE   0/313 (0.00%)  0 1/319 (0.31%)  1
Renal and urinary disorders     
DIURESIS   36/313 (11.50%)  83 44/319 (13.79%)  77
ELEVATED CREATININE   17/313 (5.43%)  26 16/319 (5.02%)  24
HYPERKALEMIA   45/313 (14.38%)  54 49/319 (15.36%)  58
GLUCOSUIRA   7/313 (2.24%)  7 2/319 (0.63%)  3
HEMATURIA   14/313 (4.47%)  16 14/319 (4.39%)  17
OLIGURIA   46/313 (14.70%)  79 46/319 (14.42%)  68
PROTEINURIA   14/313 (4.47%)  17 9/319 (2.82%)  14
RENAL DYSFUNCTION   0/313 (0.00%)  0 1/319 (0.31%)  1
RENAL FAILURE   0/313 (0.00%)  0 1/319 (0.31%)  1
BILATERAL HYDRONEPHROSIS   0/313 (0.00%)  0 1/319 (0.31%)  1
Respiratory, thoracic and mediastinal disorders     
PULMONARY AIR LEAK   23/313 (7.35%)  25 25/319 (7.84%)  28
PULMONARY HEMORRHAGE   3/313 (0.96%)  3 7/319 (2.19%)  8
RESPIRATORY DETERIORATION   114/313 (36.42%)  172 120/319 (37.62%)  171
CHRONIC LUNG DISEASE   8/313 (2.56%)  8 7/319 (2.19%)  7
RESPIRATORY DISTRESS   2/313 (0.64%)  2 0/319 (0.00%)  0
Skin and subcutaneous tissue disorders     
RASH   4/313 (1.28%)  5 5/319 (1.57%)  5
SKIN BREAKDOWN   7/313 (2.24%)  7 4/319 (1.25%)  4
IV INFILTRATE   1/313 (0.32%)  1 1/319 (0.31%)  1
SKIN LESION   0/313 (0.00%)  0 1/319 (0.31%)  1
ATOPIC DERMATITIS *  1/313 (0.32%)  1 0/319 (0.00%)  0
SOFT TISSUE NECROSIS (UPPER LIMB) *  1/313 (0.32%)  1 0/319 (0.00%)  0
NASAL SEPTIC BREAKDOWN *  1/313 (0.32%)  1 0/319 (0.00%)  0
Vascular disorders     
THROMBOSIS   2/313 (0.64%)  2 0/319 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Other (not including serious) adverse events under blood and lymphatic system disorders includes frank blood drainage from Penrose drain.
[2]
Other (not including serious) adverse events under cardiac disorders include atrial vegetation/thrombus, femoral continuous loop complication (under perfusion right leg and great toe)
*
Indicates events were collected by non-systematic assessment
Due to a manufacturing issue, enrollment and treatment were temporarily suspended pending review of primary outcome data for the enrolled infants. The statistically significant increase in mortality resulted in early study termination.
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.
Investigators must adhere to the Neonatal Research Network Publication policies.
Results Point of Contact
Name/Title: Dale Phelps
Organization: University of Rochester
Phone: (585) 275-2972
Responsible Party: NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT01954082     History of Changes
Other Study ID Numbers: NICHD-NRN-0053
U10HD021364 ( U.S. NIH Grant/Contract )
U10HD040689 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD034216 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U10HD040492 ( U.S. NIH Grant/Contract )
U10HD053109 ( U.S. NIH Grant/Contract )
U10HD053089 ( U.S. NIH Grant/Contract )
U10HD068244 ( U.S. NIH Grant/Contract )
U10HD068263 ( U.S. NIH Grant/Contract )
U10HD068270 ( U.S. NIH Grant/Contract )
U10HD068278 ( U.S. NIH Grant/Contract )
U10HD068284 ( U.S. NIH Grant/Contract )
U10HD036790 ( U.S. NIH Grant/Contract )
First Submitted: September 26, 2013
First Posted: October 1, 2013
Results First Submitted: December 29, 2017
Results First Posted: September 26, 2018
Last Update Posted: September 26, 2018