Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)

Phase 2

Terminated

• Conditions: Hypoxic Respiratory Failure; PPHN; Persistent Pulmonary Hypertension of the Newborn
• Interventions: Drug: sildanefil

• Registration Number: NCT01069861
• Lead Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

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 Timeline

• Study First Submitted: 2010-02-15
• Study First Submitted QC: 2010-02-15
• Study First Posted: 2010-02-17
• Study Start: 2010-12
• Primary Completion: 2011-11
• Study Completion: 2011-11
• Results First Submitted: 2012-11-01
• Results First Submitted QC: 2012-11-01
• Results First Posted: 2012-12-03
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-28
• Last Update Posted: 2021-02-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
one	sildanefil	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO)	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	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	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).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Differential Saturation (Pre- And Post-ductal) at Hour 6 and 12	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	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.
Maximum Observed Plasma Concentration (Cmax) of Sildenafil Metabolite (UK-103320)	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
Population Pharmacokinetics of Sildenafil	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.
Time to Receipt of Standard Therapy (Inhaled Nitric Oxide [iNO] or Extracorporeal Membrane Oxygenation [ECMO])	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.
Change From Baseline in Oxygenation Index at Hour 6 and 12	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.
Duration of Mechanical Ventilation	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.

Trial Locations

Locations (1)

Great Ormond Street Hospital, Paediatric Intensive Care; 🇬🇧 London, United Kingdom