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Sildenofil in Persistent Pulmonary Hypertension in Newborns

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Hamad Medical Corporation
Sponsor:
Information provided by (Responsible Party):
Hamad Medical Corporation
ClinicalTrials.gov Identifier:
NCT01558466
First received: March 11, 2012
Last updated: September 23, 2012
Last verified: September 2012

March 11, 2012
September 23, 2012
November 2011
November 2014   (final data collection date for primary outcome measure)
  • Oxygen index [ Time Frame: 7 days after birth and admission to the NICU ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Alveolar arterial oxygen difference gradient
  • Hemodynamic parameters [ Time Frame: 7 days ] [ Designated as safety issue: No ]

    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

Same as current
Complete list of historical versions of study NCT01558466 on ClinicalTrials.gov Archive Site
  • Days of hospitalization [ Time Frame: 7 days after admission to the NICU ] [ Designated as safety issue: No ]
    Length of hospitalization and mortality, morbidity, ventialtion dats , adverse events
  • mortality [ Time Frame: 28 days of life ] [ Designated as safety issue: No ]
    All cause mortality within 28 days of life
Same as current
Not Provided
Not Provided
 
Sildenofil in Persistent Pulmonary Hypertension in Newborns
Early Combined Use of Inhaled Nitric Oxide and Oral Sildenafil on the Outcome of Pulmonary Hypertension in New Born Infants

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Persistent Fetal Circulation Syndrome
  • 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 Name: Viagra
  • 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 Name: Normal saline
  • Placebo Comparator: Group A - Placebo
    iNO combined with placebo will be administered
    Intervention: Drug: diluent
  • Active Comparator: Group B- Sildenafil
    iNO combined with Sildenafil
    Intervention: Drug: Sildenafil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
June 2015
November 2014   (final data collection date for primary outcome measure)

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
Both
36 Weeks to 41 Weeks
No
Contact: Husam Em Salama, MRCP 00974- 55262159 hsalama1@hmc.org.qa
Contact: Ahmed Masoud, MD 00974-55112369 amasoud@hmc.org.qa
Qatar
 
NCT01558466
10228/10
No
Hamad Medical Corporation
Hamad Medical Corporation
Not Provided
Principal Investigator: Husam Salama, MD Hamad Medical Corporation, Doha, Qatar
Hamad Medical Corporation
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP