Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)
Sildenafil is efficacious in newborns with persistent pulmonary hypertension and its use will reduce the need for inhaled nitric oxide.
Persistent Pulmonary Hypertension of the Newborn
Hypoxic Respiratory Failure
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO) [ Time Frame: From start of infusion (baseline) up to Day 14 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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) ] [ Designated as safety issue: No ]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).
- Change From Baseline in Oxygenation Index at Hour 6 and 12 [ Time Frame: Baseline, Hour 6, 12 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Duration of Study Medication [ Time Frame: Baseline up to Day 14 ] [ Designated as safety issue: No ]The duration of the infusion was determined as per investigator's discretion up to Day 7 or Day 14.
|Study Start Date:||December 2010|
|Study Completion Date:||November 2011|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
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.
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.