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Sildenofil in Persistent Pulmonary Hypertension in Newborns (Sildeno)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01558466
Recruitment Status : Unknown
Verified September 2012 by Hamad Medical Corporation.
Recruitment status was:  Recruiting
First Posted : March 20, 2012
Last Update Posted : September 25, 2012
Information provided by (Responsible Party):
Hamad Medical Corporation

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : November 2011
Estimated Primary Completion Date : November 2014
Estimated Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

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 Name: 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 Name: Viagra

Primary Outcome Measures :
  1. 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.

  2. A-a gradient [ Time Frame: 7 days after admission to the NICU ]
    Alveolar arterial oxygen difference gradient

  3. 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

Secondary Outcome Measures :
  1. Days of hospitalization [ Time Frame: 7 days after admission to the NICU ]
    Length of hospitalization and mortality, morbidity, ventialtion dats , adverse events

  2. mortality [ Time Frame: 28 days of life ]
    All cause mortality within 28 days of life

Information from the National Library of Medicine

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Ages Eligible for Study:   36 Weeks to 41 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01558466

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Contact: Husam Em Salama, MRCP 00974- 55262159
Contact: Ahmed Masoud, MD 00974-55112369

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Women's hospital, NICU Recruiting
Doha, Qatar, 00974
Contact: Husam Salama, MD    552262159   
Contact: Ahmad Masoud, MD    55112369   
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         
Sponsors and Collaborators
Hamad Medical Corporation
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Principal Investigator: Husam Salama, MD Hamad Medical Corporation, Doha, Qatar

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Responsible Party: Hamad Medical Corporation Identifier: NCT01558466     History of Changes
Other Study ID Numbers: 10228/10
First Posted: March 20, 2012    Key Record Dates
Last Update Posted: September 25, 2012
Last Verified: September 2012
Keywords provided by Hamad Medical Corporation:
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Persistent Fetal Circulation Syndrome
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Infant, Newborn, Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents