Clinical trial NCT01069861: Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: PPHN
Persistent Pulmonary Hypertension of the Newborn
Hypoxic Respiratory Failure
Keywords: PPHN
neonates
sildanefil IV
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-02-17
Enrollment: 4
Sex: ALL
Minimum age (years): 1
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO)
timeFrame: From start of infusion (baseline) up to Day 14
measure: Number of Participants With Adverse Events (AEs) Based on Severity
timeFrame: Baseline up to 28 days after last dose
measure: Number of Participants With Abnormal Laboratory Data
timeFrame: Screening, once daily for 3 days, every 48 hours thereafter till the end of infusion (up to Day 14)
Secondary outcomes:
measure: Change From Baseline in Oxygenation Index at Hour 6 and 12
timeFrame: Baseline, Hour 6, 12
measure: Change From Baseline in Differential Saturation (Pre- And Post-ductal) at Hour 6 and 12
timeFrame: Baseline, Hour 6, 12
measure: 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
timeFrame: Baseline, Hour 6, 12
measure: Duration of Mechanical Ventilation
timeFrame: Baseline up to 28 days after last dose
measure: Time to Receipt of Standard Therapy (Inhaled Nitric Oxide [iNO] or Extracorporeal Membrane Oxygenation [ECMO])
timeFrame: Baseline up to 28 days after last dose
measure: Population Pharmacokinetics of Sildenafil
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Sildenafil Metabolite (UK-103320)
timeFrame: 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
Other outcomes:
measure: Duration of Study Medication
timeFrame: Baseline up to Day 14
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital, Paediatric Intensive Care
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: