Sildenofil in Persistent Pulmonary Hypertension in Newborns

NCT ID: NCT01558466

Last Updated: 2012-09-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-06-30

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.

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.

Conditions

Persistent Fetal Circulation Syndrome

Keywords

newborn; INO; Sildenafil; PPHN

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group A - Placebo

iNO combined with placebo will be administered

Group Type: PLACEBO_COMPARATOR

diluent

Intervention Type: DRUG

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

Group B- Sildenafil

iNO combined with Sildenafil

Group Type: ACTIVE_COMPARATOR

Sildenafil

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Viagra; Normal saline

Eligibility Criteria

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

• Minimum Eligible Age: 36 Weeks
• Maximum Eligible Age: 41 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamad Medical Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Husam Salama, MD

Role: PRINCIPAL_INVESTIGATOR

Hamad Medical Corporation, Doha, Qatar

Locations

Women's hospital, NICU

Doha, Qatar, Qatar

Site Status: RECRUITING

Countries

Qatar

Central Contacts

Husam Em Salama, MRCP

Role: CONTACT

Phone: 00974- 55262159

Email: hsalama1@hmc.org.qa

Ahmed Masoud, MD

Role: CONTACT

Phone: 00974-55112369

Email: amasoud@hmc.org.qa

Facility Contacts

Husam Salama, MD

Role: primary

Ahmad Masoud, MD

Role: backup

Other Identifiers

10228/10

Identifier Type: -

Identifier Source: org_study_id