Persistent Fetal Circulation SyndromePhase 3SildenoNCT01558466
Sildenofil in Persistent Pulmonary Hypertension in Newborns
A Phase 3 study testing Sildenafil and diluent in people with Persistent Fetal Circulation Syndrome, run by Hamad Medical Corporation at 1 site in Qatar.
Trial 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… Read more about this study
- Who is it for?
- Ages 36 to 41 weeks
- Conditions the study is for
- Persistent Fetal Circulation Syndrome
- What is being tested?
- Sildenafil and diluent
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteQatar
- Study dates
- Nov 2011to Jun 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 36 to 41 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Newborn infants of post natal age less than 48 hours
- Gestational age equal to or more than 34 weeks
- Oxygen index of more than or equal to 20 (moderately ill infants)
- Radiological, clinical and biochemical evidence of acute hypoxic respiratory failure
- Surfactant therapy has been established when indicated
- Presence of arterial line
Who cannot join
- Congenital diaphragmatic hernia
- Major congenital abnormalities
- Significant congenital heart disease
- Cyanotic congenital heart disease
Trial locations and contacts
1 site in 1 country.
Qatar1 site, 1 recruiting
- Recruiting
Women's hospital, NICU
Doha, Qatar, 00974
Husam Salama, MD, 552262159, hsalama1@hmc.org.qa
Ahmad Masoud, MD, 55112369, amasoud@hmc.org.qa
About this study
Official title: 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.
Read the 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
- Being tested
- Sildenafil, diluent
- Keywords
- newborn, INO, Sildenafil, PPHN
- Medical subject headings
- Persistent Fetal Circulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Viagra
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.
diluentDrug
Also called Normal saline
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
| Study group | Role | What they receive |
|---|---|---|
| Group A - Placebo | Placebo comparator | iNO combined with placebo will be administered Receives: Drug: diluent |
| Group B- Sildenafil | Active comparator | iNO combined with Sildenafil Receives: Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxygen index
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.
Measured: 7 days after birth and admission to the NICU
A-a gradient
Alveolar arterial oxygen difference gradient
Measured: 7 days after admission to the NICU
Hemodynamic parameters
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 :
- 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
Measured: 7 days
Secondary outcomes (2)
Days of hospitalization
Length of hospitalization and mortality, morbidity, ventialtion dats , adverse events
Measured: 7 days after admission to the NICU
mortality
All cause mortality within 28 days of life
Measured: 28 days of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2012 (estimated)
- Study startNov 2011
- Primary completionNov 2014 (estimated)
- Study completionJun 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Persistent Fetal Circulation SyndromeStudies of the same condition, open and under way.
- More trials run by Hamad Medical CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamad Medical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Husam Salama, MD, Principal investigator, Hamad Medical Corporation, Doha, Qatar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01558466
- Sponsor's protocol ID
- 10228/10
- Acronym
- Sildeno
- Status last verified
- Sep 2012
- First submitted
- 11 Mar 2012
- Last updated
- 25 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Combined Use of Inhaled Nitric Oxide and Oral Sildenafil on the Outcome of Pulmonary Hypertension in New Born Infants
- ClinicalTrials.gov ID
- NCT01558466
- Acronym / sponsor ID
- Sildeno / 10228/10
- Conditions
- Persistent Fetal Circulation Syndrome
- Keywords
- newborn, INO, Sildenafil, PPHN
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Hamad Medical CorporationIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Nov 2014 (estimated)
- Study completion
- Jun 2015 (estimated)
- First posted
- 20 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A - Placebo | Placebo comparator | Drug: diluentiNO combined with placebo will be administered |
| Group B- Sildenafil | Active comparator | Drug: SildenafiliNO combined with Sildenafil |
Who may qualify
- Ages
- 36 to 41 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Newborn infants of post natal age less than 48 hours
- Gestational age equal to or more than 34 weeks
- Oxygen index of more than or equal to 20 (moderately ill infants)
- Radiological, clinical and biochemical evidence of acute hypoxic respiratory failure
- Surfactant therapy has been established when indicated
Key exclusion criteria (4 listed)
- Congenital diaphragmatic hernia
- Major congenital abnormalities
- Significant congenital heart disease
- Cyanotic congenital heart disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SildenafilAlso: Viagra50 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. | Drug | Group B- Sildenafil |
| diluentAlso: Normal salineThe 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 | Drug | Group A - Placebo |
Primary outcome
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
2 secondary outcomes
Days of hospitalization
Time frame: 7 days after admission to the NICU
mortality
Time frame: 28 days of life
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2012.
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Post Market Clinical Follow-up to Assess the Portable Nitric Oxide Generation and Delivery System (INOwill N200) for the Treatment of Neonatal Hypoxic Respiratory Failure Complicated by Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
Recruiting
Close Loop Smart Weaning for INO With PPHN
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Active, not recruiting
Preductal Oxygen Saturation Target in Term and Late Preterm Neonates With Hypoxemic Respiratory Failure or Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxemic Respiratory Failure
RecruitingObservational study
PTGS1 Genetic Variation and Increased Risk for Persistent Pulmonary Hypertension of the Newborn
Persistent Pulmonary Hypertension of the Newborn
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Husam Salama, MD principal investigator
Hamad Medical Corporation, Doha, Qatar
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sildenafil and diluent in people with Persistent Fetal Circulation Syndrome, run by Hamad Medical Corporation at 1 site in Qatar.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Qatar. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Husam Em Salama, MRCP (00974- 55262159, hsalama1@hmc.org.qa), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oxygen index (time frame: 7 days after birth and admission to the NICU). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2012.