Sildenofil in Persistent Pulmonary Hypertension in Newborns

Sponsor

Hamad Medical Corporation (Industry)

Overall Status

Unknown status

CT.gov ID

NCT01558466

Collaborator

(none)

100

Enrollment

Location

Arms

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study hopes to evaluate the effectiveness of early combined use of Sildenafil and nitric oxide (iNO) in newborns with Persistent pulmonary hypertension (PPHN) and or hypoxemic respiratory failure and assess whether this would improve oxygenation, improve time on mechanical ventilation for these babies and also prevent rebound hypoxic episodes.

Condition or Disease	Intervention/Treatment	Phase
Persistent Fetal Circulation Syndrome	Drug: Sildenafil Drug: diluent	Phase 3

Detailed Description

PPHN is characterized by hyper reactivity of the muscle layer in pulmonary arterioles and right to left shunt across the ductus arteriosus and the foramen ovale in the absence of structural heart defects. It could also include right ventricle dysfunction in many cases. The reported incidence of this disease is 0.43 to 6.8/1000 live new born infants with a mortality of 10-20%.

The main objective of therapy in PPHN is to reduce pulmonary vascular resistance. To this purpose, inhaled nitric oxide has been used in developed and several under developed countries. However 30-40% of these patients do not respond to this therapy. Extra corporeal membrane oxygenation is also useful but is an invasive therapy in PPHN with serious adverse effects reported. Recently Sildenafil has been evaluated as an alternative or adjunctive pulmonary vasodilator. It inhibits phosphodiesterase type 5 and elevates the concentration of cyclic guanosine monophosphate in the muscle cells of pulmonary vessels, which in turn decreases pulmonary vascular resistance.

The FDA in the USA has recently approved the use of Sildenafil for use in adults with PPHN.

Recently 3 clinical trials have evaluated Sildenafil versus Placebo or control in newborns with PPHN,all of them showing a significant improvement in oxygenation index, decreased mortality and reduced risk of rebounds after discontinuing iNO. The use of Sildenafil in treating PPHN secondary to Chronic lung disease in older infants had been receiving significant attention over the last few years.

At HMC, Women's hospital, the number of deliveries average 15,000 to 16,000 per year with an admission rate to the NICU of about 10%. The number of PPHN cases admitted to our NICU ranges between 14-20 cases per year.

In this study the investigators plan to compare the effectiveness of the use of early combined Sildenafil and iNO in newborns with PPHN and or hypoxemic respiratory failure and whether it would improve oxygenation, decrease the time spent in mechanical ventilation and prevent rebound hypoxic episodes.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Early Combined Use of Inhaled Nitric Oxide and Oral Sildenafil on the Outcome of Pulmonary Hypertension in New Born Infants

Study Start Date :

Nov 1, 2011

Anticipated Primary Completion Date :

Nov 1, 2014

Anticipated Study Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Group A - Placebo iNO combined with placebo will be administered	Drug: diluent The placebo will have an equal volume of diluent - Orabase syrup of the same colour and viscosity as the active comparator. Infants in this group will receive normal saline as placebo every 6 hours Other Names: Normal saline
Active Comparator: Group B- Sildenafil iNO combined with Sildenafil	Drug: Sildenafil 50 mg tablet will be thoroughly crushed into powder form and diluted in 10 ml ora base suspension syrup agent and a dilution will be performed to prepare 5 mg/ml. All doses required for 48 hours will be available; solutions will be stored at 2-8 degrees C where solution should be stable for at least a month. Other Names: Viagra

Arm

Intervention/Treatment

Placebo Comparator: Group A - Placebo

iNO combined with placebo will be administered

Drug: diluent

The placebo will have an equal volume of diluent - Orabase syrup of the same colour and viscosity as the active comparator. Infants in this group will receive normal saline as placebo every 6 hours

Other Names:

Normal saline

Active Comparator: Group B- Sildenafil

iNO combined with Sildenafil

Drug: Sildenafil

50 mg tablet will be thoroughly crushed into powder form and diluted in 10 ml ora base suspension syrup agent and a dilution will be performed to prepare 5 mg/ml. All doses required for 48 hours will be available; solutions will be stored at 2-8 degrees C where solution should be stable for at least a month.

Other Names:

Viagra

Outcome Measures

Primary Outcome Measures

Oxygen index [7 days after birth and admission to the NICU]
OI= PaO2 X FiO2/100( Absolute values and change from baseline measurement after first dose, measured every 6 hours for 7 days while on therapy. Improvement in OI is defined as decrease in OI of 20% from the previously calculated value.
A-a gradient [7 days after admission to the NICU]
Alveolar arterial oxygen difference gradient
Hemodynamic parameters [7 days]
Hemodynamic parameters ( absolute values and change from baseline measured after the first dose, after 24 hours, after 36 hours, and after 48 hours and every 12 hours thereafter for a total of 7 days while receiving therapy and 7 days after the end of treatment including : 1. Heart rate, mean blood pressure, respiratory rate, oxygen saturation and blood gas b. Pulmonary arterial pressure in mm Hg measured by echocardiography c. cArdiac output in liter/kg/min d. Oxygenation ( PaO2) and FiO2 requirement

Secondary Outcome Measures

Days of hospitalization [7 days after admission to the NICU]
Length of hospitalization and mortality, morbidity, ventialtion dats , adverse events
mortality [28 days of life]
All cause mortality within 28 days of life

Eligibility Criteria

Criteria

Ages Eligible for Study:

36 Weeks to 41 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Newborn infants of post natal age less than 48 hours
Gestational age equal to or more than 34 weeks
Oxygen index of more than or equal to 20 (moderately ill infants)
Radiological, clinical and biochemical evidence of acute hypoxic respiratory failure
Surfactant therapy has been established when indicated
Presence of arterial line