Hernia, DiaphragmaticPhase 4NCT00133679
Chronic Sildenafil for Severe Diaphragmatic Hernia
A Phase 4 study testing sildenafil in people with Hernia, Diaphragmatic and Hypertension, Pulmonary, run by University of California, San Francisco at 3 sites in United States.
Trial summary
The purpose of this study is to test if sildenafil is effective in the treatment of infants with severe congenital diaphragmatic hernia (determined by the presence of prolonged pulmonary hypertension or prolonged oxygen supplementation on mechanical ventilation), as measured by the estimated pulmonary artery systolic… Read more about this study
- Who is it for?
- Ages 10 to 42 days
- Conditions the study is for
- Hernia, Diaphragmatic, Hypertension, Pulmonary, Hypoplasia, Pulmonary
- What is being tested?
- sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2006to Oct 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 10 to 42 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Congenital diaphragmatic hernia
- 10-42 days (d) of age
- Significant illness severity as demonstrated by:
- Receiving assisted ventilation and
- FiO2 >= 0.40 at 10-14d of age, or
- FiO2 >= 0.40 for >=48hours at 15-27d of age, or
Show all 9Show fewer
- FiO2 >= 0.35 at 28-42d of age
- Or, need for extracorporeal support at >=10d of age
- Or, estimated pulmonary arterial or right ventricular systolic pressure of >= 2/3 systemic pressure at 14-42d of age
Who cannot join
- Structural congenital heart disease (other than patent ductus arteriosus or patent foramen ovale/atrial septal defect [ASD] or non-hemodynamically significant ventricular septal defect [VSD])
- Sildenafil contraindicated (until condition resolves):
- Unable to absorb oral medication, or
- Unstable systemic blood pressure, or
- Receiving a drug that may interfere with sildenafil metabolism, or
- Renal insufficiency
- Hepatic insufficiency Previous use of sildenafil
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Children's Memorial Hospital
Chicago, Illinois, 60614
Children's Hospital of Los Angeles
Los Angeles, California, 90027
University of California San Francisco Children's Hospital
San Francisco, California, 94143
About this study
The purpose of this study is to test if sildenafil is effective in the treatment of infants with severe congenital diaphragmatic hernia (determined by the presence of prolonged pulmonary hypertension or prolonged oxygen supplementation on mechanical ventilation), as measured by the estimated pulmonary artery systolic pressure following treatment.
Read the detailed description
Congenital diaphragmatic hernia (CDH) is a condition characterized by pulmonary parenchymal and vascular hypoplasia. Severe CDH carries a high rate of mortality, and significant morbidity among survivors. This proposal is a randomized, blinded, placebo-controlled study designed to evaluate the efficacy and potential mechanisms of activity of sildenafil, a phosphodiesterase-5 inhibitor, for treatment of severe CDH. Infants who meet criteria at ≥10d of age predicting a poor outcome [death or chronic lung disease (CLD) severe enough to require hospital discharge on supplemental oxygen (O2)] will be eligible for the study. Infants whose parents consent for the study will undergo an initial echocardiogram to assess the degree of pulmonary hypertension. They will then begin either sildenafil or placebo therapy for a 45d course. A final echocardiogram will be performed after the experimental drug course is completed. The pulmonary arterial systolic pressure estimate during hyperoxic conditions will be compared between the sildenafil and placebo groups. Infants from either group who have severely elevated pulmonary arterial pressure (despite supplemental O2) will be considered for open-label sildenafil, which will continue after hospital discharge, depending on the results of a cardiac catheterization performed for clinical care.
- Being tested
- sildenafil, Placebo
- Keywords
- Chronic lung disease, Nitric oxide, cyclic guanosine monophosphate, phosphodiesterase inhibitor
- Medical subject headings
- Hernia, Diaphragmatic, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sildenafilDrug
Also called Viagra, Revatio
Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
PlaceboDrug
Placebo suspension (equal volume to experimental drug) x 45 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Sildenafil x 45 days Receives: Drug: sildenafil |
| 2 | Placebo comparator | Placebo x 45 d Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram
Measured: 7 weeks
Secondary outcomes (5)
Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram
Measured: 7 weeks
Adverse Effects of Sildenafil Therapy
Measured: 2 years
Somatic Growth at 1 and 2 Years of Age
Measured: 2 years
Neurodevelopmental Outcome at 1 and 2 Years of Age
Measured: 2 years
Respiratory Status at 1 and 2 Years of Age
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2005 (estimated)
- Study startFeb 2006
- Primary completionJul 2013
- Study completionOct 2013
Why it stopped: Change in clinical practice allowing chronic therapy at 6 weeks of age, incompatible with possibility of placebo beyond 6 weeks of age on study protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hernia, DiaphragmaticStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Los Angeles, Ann & Robert H Lurie Children's Hospital of Chicago
- Responsible party
- Sponsor
- Investigators
- Roberta L Keller, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00133679
- Sponsor's protocol ID
- K23HL079922-01
- Status last verified
- Jan 2021
- First submitted
- 22 Aug 2005
- Last updated
- 13 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronic Sildenafil for Severe Diaphragmatic Hernia
- ClinicalTrials.gov ID
- NCT00133679
- Acronym / sponsor ID
- K23HL079922-01
- Keywords
- Chronic lung disease, Nitric oxide, cyclic guanosine monophosphate, phosphodiesterase inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Change in clinical practice allowing chronic therapy at 6 weeks of age, incompatible with possibility of placebo beyond 6 weeks of age on study protocol
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Children's Hospital Los Angeles, Ann & Robert H Lurie Children's Hospital of Chicago
- Study start
- Feb 2006
- Primary completion
- Jul 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 23 Aug 2005 (estimated)
- Results
- Posted 13 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test if sildenafil is effective in the treatment of infants with severe congenital diaphragmatic hernia (determined by the presence of prolonged pulmonary hypertension or prolonged oxygen supplementation on mechanical ventilation), as measured by the estimated pulmonary artery systolic pressure following treatment.
Detailed description
Congenital diaphragmatic hernia (CDH) is a condition characterized by pulmonary parenchymal and vascular hypoplasia. Severe CDH carries a high rate of mortality, and significant morbidity among survivors. This proposal is a randomized, blinded, placebo-controlled study designed to evaluate the efficacy and potential mechanisms of activity of sildenafil, a phosphodiesterase-5 inhibitor, for treatment of severe CDH. Infants who meet criteria at ≥10d of age predicting a poor outcome [death or chronic lung disease (CLD) severe enough to require hospital discharge on supplemental oxygen (O2)] will be eligible for the study. Infants whose parents consent for the study will undergo an initial echocardiogram to assess the degree of pulmonary hypertension. They will then begin either sildenafil or placebo therapy for a 45d course. A final echocardiogram will be performed after the experimental drug course is completed. The pulmonary arterial systolic pressure estimate during hyperoxic conditions will be compared between the sildenafil and placebo groups. Infants from either group who have severely elevated pulmonary arterial pressure (despite supplemental O2) will be considered for open-label sildenafil, which will continue after hospital discharge, depending on the results of a cardiac catheterization performed for clinical care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: sildenafilSildenafil x 45 days |
| 2 | Placebo comparator | Drug: PlaceboPlacebo x 45 d |
Who may qualify
- Ages
- 10 to 42 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Congenital diaphragmatic hernia
- 10-42 days (d) of age
- Significant illness severity as demonstrated by:
- Receiving assisted ventilation and
- Or, need for extracorporeal support at >=10d of age
Key exclusion criteria (7 listed)
- Structural congenital heart disease (other than patent ductus arteriosus or patent foramen ovale/atrial septal defect [ASD] or non-hemodynamically significant ventricular septal defect [VSD])
- Sildenafil contraindicated (until condition resolves):
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: Viagra, RevatioSildenafil 0.5 mg/kg every 6 hours orally x 45 d | Drug | 1 |
| PlaceboPlacebo suspension (equal volume to experimental drug) x 45 days | Drug | 2 |
Primary outcome
Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram
Time frame: 7 weeks
5 secondary outcomes
Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram
Time frame: 7 weeks
Adverse Effects of Sildenafil Therapy
Time frame: 2 years
Somatic Growth at 1 and 2 Years of Age
Time frame: 2 years
Neurodevelopmental Outcome at 1 and 2 Years of Age
Time frame: 2 years
Respiratory Status at 1 and 2 Years of Age
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Roberta L Keller, MD principal investigator
University of California, San Francisco
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sildenafil in people with Hernia, Diaphragmatic and Hypertension, Pulmonary, run by University of California, San Francisco at 3 sites in United States.
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 9 inclusion and 7 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: stopped early, as of the sponsor's last update on 13 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram (time frame: 7 weeks). 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 13 Jan 2021.