Trial Outcomes & Findings for Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN) (NCT NCT01069861)

Results Overview

Percentage of participants who required standard therapy (iNO or ECMO) after failure of study treatment.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

From start of infusion (baseline) up to Day 14

Results posted on

2021-02-01

Participant Flow

Participant milestones

Participant milestones
Measure	Sildenafil Sildenafil citrate administered intravenously at a loading dose of 0.1 milligram per kilogram (mg/kg) over 30 minutes infusion followed by a maintenance dose of 0.03 mg/kg per hour (mg/kg/hr) intravenous infusion up to 14 days, based on the need of individual participant.
Overall Study STARTED	4
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Sildenafil Sildenafil citrate administered intravenously at a loading dose of 0.1 milligram per kilogram (mg/kg) over 30 minutes infusion followed by a maintenance dose of 0.03 mg/kg per hour (mg/kg/hr) intravenous infusion up to 14 days, based on the need of individual participant.
Overall Study Death	1
Overall Study Adverse Event	1
Overall Study Did not meet entrance criteria	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sildenafil n=4 Participants Sildenafil citrate administered intravenously at a loading dose of 0.1 mg/kg over 30 minutes infusion followed by a maintenance dose of 0.03 mg/kg/hr intravenous infusion up to 14 days, based on the need of individual participant.
Age, Continuous	1.5 days STANDARD_DEVIATION 0.5 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start of infusion (baseline) up to Day 14

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

Percentage of participants who required standard therapy (iNO or ECMO) after failure of study treatment.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline up to 28 days after last dose

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

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".

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Screening, once daily for 3 days, every 48 hours thereafter till the end of infusion (up to Day 14)

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Hour 6, 12

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Hour 6, 12

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Hour 6, 12

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 14

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

The duration of the infusion was determined as per investigator's discretion up to Day 7 or Day 14.

Outcome measures

Outcome data not reported

Adverse Events

Sildenafil

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sildenafil n=4 participants at risk Sildenafil citrate administered intravenously at a loading dose of 0.1 mg/kg over 30 minutes infusion followed by a maintenance dose of 0.03 mg/kg/hr intravenous infusion up to 14 days, based on the need of individual participant.
Congenital, familial and genetic disorders Congenital pneumonia	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Congenital, familial and genetic disorders Persistent foetal circulation	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Other adverse events
Measure	Sildenafil n=4 participants at risk Sildenafil citrate administered intravenously at a loading dose of 0.1 mg/kg over 30 minutes infusion followed by a maintenance dose of 0.03 mg/kg/hr intravenous infusion up to 14 days, based on the need of individual participant.
Cardiac disorders Cardiac disorder	50.0% 2/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Pericardial effusion	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Infusion site erythema	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Incorrect drug administration duration	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood lactic acid increased	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations C-reactive protein increased	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Intraventricular haemorrhage	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	50.0% 2/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Blister	25.0% 1/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypotension	50.0% 2/4 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER