Sildenofil in Persistent Pulmonary Hypertension in Newborns (Sildeno)
Recruitment status was: Recruiting
|Persistent Fetal Circulation Syndrome||Drug: Sildenafil Drug: diluent||Phase 3|
|Study Design:||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|
- Oxygen index [ Time Frame: 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 [ Time Frame: 7 days after admission to the NICU ]Alveolar arterial oxygen difference gradient
- Hemodynamic parameters [ Time Frame: 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
- Days of hospitalization [ Time Frame: 7 days after admission to the NICU ]Length of hospitalization and mortality, morbidity, ventialtion dats , adverse events
- mortality [ Time Frame: 28 days of life ]All cause mortality within 28 days of life
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Placebo Comparator: Group A - Placebo
iNO combined with placebo will be administered
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 Name: Normal saline
Active Comparator: Group B- Sildenafil
iNO combined with 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 Name: Viagra
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01558466
|Contact: Husam Em Salama, MRCP||00974- email@example.com|
|Contact: Ahmed Masoud, MDfirstname.lastname@example.org|
|Women's hospital, NICU||Recruiting|
|Doha, Qatar, 00974|
|Contact: Husam Salama, MD 552262159 email@example.com|
|Contact: Ahmad Masoud, MD 55112369 firstname.lastname@example.org|
|Principal Investigator: Husam Salama, MD|
|Principal Investigator: Ahmad Masoud, MD|
|Sub-Investigator: Moza Al Hail, BpH|
|Sub-Investigator: Hilal Al Rifai, MD|
|Sub-Investigator: Mohamed Bunaiha, BpH|
|Sub-Investigator: Samawal Lutfi, MD|
|Sub-Investigator: Mohamad Delawar, MD|
|Sub-Investigator: Badr Kurdi, MD|
|Sub-Investigator: Afif Ali, B.PH|
|Sub-Investigator: Robert Hightree, RT|
|Sub-Investigator: Ghassan Abdoh, MD|
|Sub-Investigator: Samer Taha, Fellowship|
|Principal Investigator:||Husam Salama, MD||Hamad Medical Corporation, Doha, Qatar|