Sildenofil in Persistent Pulmonary Hypertension in Newborns

Hamad Medical Corporation (HMC)

Status and phase: Unknown; Phase 3

Conditions: Persistent Fetal Circulation Syndrome

Treatments: Drug: diluent; Drug: Sildenafil

Study type: Interventional

Funder types: Industry

Identifiers

NCT01558466

10228/10

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 36 to 41 weeks old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Congenital diaphragmatic hernia
2. Major congenital abnormalities
3. Significant congenital heart disease
4. Cyanotic congenital heart disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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100 participants in 2 patient groups, including a placebo group

Group A - Placebo

Placebo Comparator group

Description:

iNO combined with placebo will be administered

Treatment:

Drug: diluent

Group B- Sildenafil

Active Comparator group

Description:

iNO combined with Sildenafil

Treatment:

Drug: Sildenafil