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Trial record 1 of 2 for:    NCT01069861
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Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)

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ClinicalTrials.gov Identifier: NCT01069861
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : February 17, 2010
Results First Posted : December 3, 2012
Last Update Posted : December 3, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 15, 2010
First Posted Date  ICMJE February 17, 2010
Results First Submitted Date  ICMJE November 1, 2012
Results First Posted Date  ICMJE December 3, 2012
Last Update Posted Date December 3, 2012
Study Start Date  ICMJE December 2010
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2012)
  • Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO) [ Time Frame: From start of infusion (baseline) up to Day 14 ]
    Percentage of participants who required standard therapy (iNO or ECMO) after failure of study treatment.
  • Number of Participants With Adverse Events (AEs) Based on Severity [ Time Frame: Baseline up to 28 days after last dose ]
    AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE:AE resulting in any of following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience; persistent/significant disability/incapacity; congenital anomaly. Severity criteria: "mild=does not interfere with participant's usual function; moderate=interferes to some extent with participant's usual function and severe=interferes significantly with participant's usual function".
  • Number of Participants With Abnormal Laboratory Data [ Time Frame: Screening, once daily for 3 days, every 48 hours thereafter till the end of infusion (up to Day 14) ]
    Criteria for potentially clinically significant (PCS) laboratory values: hematocrit 29.2 percent (%); white blood cell (WBC) count 5.0*10^3, lymphocyte absolute 0.88*10^3, total neutrophils absolute 12.07*10^3, eosinophils absolute 0.50*10^3 per cubic millimeter (/mm^3); calcium 6.8 milligram/deciliter (mg/dL); venous bicarbonate 47.0 milliequivalent/liter (meq/L).
Original Primary Outcome Measures  ICMJE
 (submitted: February 15, 2010)
  • Efficacy - incidence of treatment failure: -Need for an inhaled nitric oxide (iNO) or extracorporeal membrane oxygenation (ECMO). [ Time Frame: 14 days ]
  • Safety: the following data will be used to assess the safety of IV sildenafil in this patient population: -Incidence and severity of adverse events. -Laboratory parameters [ Time Frame: 14 days ]
Change History Complete list of historical versions of study NCT01069861 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2012)
  • Change From Baseline in Oxygenation Index at Hour 6 and 12 [ Time Frame: Baseline, Hour 6, 12 ]
    Oxygenation Index (OI) was calculated as the product of fraction of inspired oxygen (FiO2) and Mean Airway Pressure divided by partial pressure of oxygen in arterial blood [(FiO2*Mean Airway Pressure)/PaO2] measured in centimeter of water/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 in the arterial blood.
  • Change From Baseline in Differential Saturation (Pre- And Post-ductal) at Hour 6 and 12 [ Time Frame: Baseline, Hour 6, 12 ]
    Differential oxygenation saturation between preductal and postductal sites as measured by pulse oximetry. A difference of greater than (>) 5 percent (%) to 10% in saturation indicates right-to-left shunt through the ductus arteriosus. Oxygenation saturation is measured as percentage of hemoglobin binding sites occupied by oxygen in the blood.
  • Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to the Fraction of Inspired Oxygen (P/F) at Hour 6 and 12 [ Time Frame: Baseline, Hour 6, 12 ]
    The ratio of partial pressure of arterial oxygen and fraction of inspired oxygen is a comparison 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.
  • Duration of Mechanical Ventilation [ Time Frame: Baseline up to 28 days after last dose ]
    The number of days from the start to the stop of mechanical ventilation, if multiple ventilations occurred during the follow-up, the sum of the duration of each ventilation was used for analyses. Mechanical ventilation was defined as use of mechanical assistance or replacement of spontaneous breathing.
  • Time to Receipt of Standard Therapy (Inhaled Nitric Oxide [iNO] or Extracorporeal Membrane Oxygenation [ECMO]) [ Time Frame: Baseline up to 28 days after last dose ]
    Time from start of treatment up to introduction of standard therapy. If participants did not receive standard therapy within 14 days after initiation of the study treatment, then Day 14 was the censoring time.
  • Population Pharmacokinetics of Sildenafil [ Time Frame: Pre-dose, 5 and 30 minutes post-loading infusion, within 48 to 72, 96 to 120 hours during infusion, within 4 to 8, 18 to 24 and 44 to 48 hours post-maintenance infusion ]
    Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
  • Maximum Observed Plasma Concentration (Cmax) of Sildenafil Metabolite (UK-103320) [ Time Frame: Pre-dose, 5 and 30 minutes post-loading infusion, within 48 to 72, 96 to 120 hours during infusion, within 4 to 8, 18 to 24 and 44 to 48 hours post-maintenance infusion ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2010)
  • Changes in oxygenation index at 6 and 12 hours post baseline. Therapy (iNO or ECMO). [ Time Frame: 6h; 12h ]
  • Change in differential saturation (pre- and post-ductal) at 6 and 12 hours post baseline [ Time Frame: 6h ;12h ]
  • Change in P/F ratio at 6 and 12 hours post baseline. [ Time Frame: 6h;12h ]
  • Duration (in days) of mechanical ventilation. [ Time Frame: 14 days ]
  • Time from initiation of study drug to receipt of additional standard therapy [ Time Frame: 14 days ]
  • Duration (in hours) of sildenafil therapy. [ Time Frame: 14 days ]
Current Other Pre-specified Outcome Measures
 (submitted: November 1, 2012)
Duration of Study Medication [ Time Frame: Baseline up to Day 14 ]
The duration of the infusion was determined as per investigator's discretion up to Day 7 or Day 14.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)
Official Title  ICMJE A Single Arm Single Centre Study To Investigate Safety And Efficacy Of Sildenafil In Near Term And Term Newborns With Persistent Pulmonary Hypertension Of The Newborn (PPHN)
Brief Summary Sildenafil is efficacious in newborns with persistent pulmonary hypertension and its use will reduce the need for inhaled nitric oxide.
Detailed Description Letter to investigator dated 18 June 2012 that study was to be terminated. Study terminated due to evolved and widespread use of standard of care, relevance of study questioned. No safety reasons or issues.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • PPHN
  • Persistent Pulmonary Hypertension of the Newborn
  • Hypoxic Respiratory Failure
Intervention  ICMJE Drug: sildanefil
Intravenous sildenafil citrate will be administered as a loading dose of 0.1 mg/kg given over 30 minutes. This will be followed by a maintenance treatment consisting of an intravenous infusion of 0.03 mg/kg/hr. The duration of the infusion will be determined by the need of the individual patient, but will be reviewed at Day 7 if still ongoing, and will not continue past Day 14.
Study Arms  ICMJE Experimental: one
Intervention: Drug: sildanefil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 22, 2012)
4
Original Estimated Enrollment  ICMJE
 (submitted: February 15, 2010)
40
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 72 hours of age; and > or = to 34 weeks gestational age.
  • Persistent Pulmonary Hypertension of the Newborn or Hypoxic respiratory failure associated with:

    1. Idiopathic PPHN or
    2. Meconium aspiration syndrome or
    3. Sepsis or
    4. Pneumonia
  • Oxygenation Index (OI) >15 and <60 calculated

Exclusion Criteria:

  • Patients already receiving inhaled nitric oxide (iNO) on referral.
  • Prior or immediate need for full Cardio Pulmonary Resuscitation or Extracorporeal Membrane Oxygenation (ECMO).
  • Life threatening or lethal congenital anomaly.
  • Large left to right intracardiac or ductal shunting (diagnosed from echocardiogram on admission to GOSH).
  • Clinically significant active seizures as per clinical judgment.
  • Bleeding diathesis as per clinical judgment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 72 Hours   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01069861
Other Study ID Numbers  ICMJE A1481276
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP