Peripheral Pulmonary StenosisPhase 2NCT02365415
Systemic Rapamycin (Sirolimus) to Prevent In-Stent Restenosis Following Pulmonary Artery Stent Placement
A Phase 2 study testing Sirolimus in people with Peripheral Pulmonary Stenosis and In-stent Stenosis, run by Boston Children's Hospital at 1 site in United States.
Trial summary
This is a research study to assess whether an oral medication can benefit some patients being treated for peripheral pulmonary stenosis (PPS), which is narrowing of the blood vessels that send blood to the lungs (pulmonary arteries). Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Peripheral Pulmonary Stenosis, In-stent Stenosis
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Apr 2018
- Phase
- Phase 2
- 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- In-stent stenosis: At least one stent from at least one prior catheterization affected by in-stent stenosis (≥25% stenosis and a diameter narrower or equal to the distal vessel).
- At least one of the following:
- RV hypertension: At least one half systemic RVp or ≥ 70 mm Hg by echocardiogram or per baseline hemodynamics on most recent catheterization
- Pulmonary blood flow maldistribution: ≤ 25% of flow to either lung or regional decrease in individual lobar segments.
- Pulmonary hypertension: Mean PA pressure ≥ 20 mmHg in unobstructed segments by most recent catheterization.
- Informed consent of patient and/or parent/guardian
- Agreement to participate in protocol, including follow-up testing
Who cannot join
- Age ≤ 6 months
- Pulmonary artery surgery or transcatheter PA dilations in the past 6 weeks.
- Malignancy (past or present)
- Active infection
- Pregnancy (current or planned within the next 1 year)
- Organ dysfunction as evidenced by laboratory abnormalities
Show all 11Show fewer
- Renal: BUN > 40 mg/dL, or Cr > normal limit for age (by powerchart). Exceptions can be made at the discretion of the study physician if BUN or Cr elevation is known to be due to diuretic management with plan to reduce dosing, or other reversible mechanism.
- Hepatic: AST or ALT > 120 unit/L, or total bilirubin > 3 mg/dL
- Immune: WBC < 2,000, or ANC or ALC < 1,000
- Hematologic: Hgb< 7 g/dL, or Hct< 21%, or platelet count < 80,000. Exceptions can be made at the discretion of the study physician if plans include transfusion of blood products in the catheterization laboratory and a known reversible etiology for the anemia.
- Lipids: Total cholesterol > 250 mg/dL, HDL < 30 g/dL
Trial locations and contacts
1 site in 1 country.
United States1 site
Boston Children's Hospital
Boston, Massachusetts, 02115
About this study
This is a research study to assess whether an oral medication can benefit some patients being treated for peripheral pulmonary stenosis (PPS), which is narrowing of the blood vessels that send blood to the lungs (pulmonary arteries).
In the cardiac catheterization laboratory, the investigators treat PPS by dilating the narrowed segments of pulmonary arteries using balloon catheters. Sometimes the investigators also place stents which are mesh tubes that help keep the narrowed vessel open. Some stents suffer from in-growth of tissue into the stents which causes recurrent obstructions inside the stent (i.e. making the opening inside the mesh tube narrow again), so called in-stent stenosis (ISS).
Read more
The purpose of this study is to use a medication that is approved for use in children (for a different purpose) to decrease the amount of cell ingrowth inside the stents (i.e. decrease the problematic in-stent stenosis). The medication is called rapamycin, also known as sirolimus (trade name Rapamune). It has antiproliferative properties which means that it slows down cell division which the investigators believe cause the recurrent narrowing inside stents.
Rapamycin is a medicine that can be taken by mouth as a liquid or pill or via a feeding tube. There will still be a need for interventions in the catheterization laboratory but the investigators hope that by taking this medicine some children would need fewer catheterizations in the future. Our early experiences with a few patients who have been treated with rapamycin due to in-stent stenosis in the pulmonary arteries suggest that it may be helpful.
In this study, patients and families who are interested in possibly trying this new approach will be randomized to sirolimus or no sirolimus. The investigators will compare the developement of ISS over time between these groups, in a hope to learn whether oral sirolimus reduces ISS development.
Read the detailed description
This is a research study to assess whether an oral medication can benefit some patients being treated for peripheral pulmonary stenosis (PPS). PPS, which can be associated with several different congenital heart diseases, is narrowing of the blood vessels that send blood to the lungs (pulmonary arteries) to pick up oxygen before returning the blood to the heart and the rest of the body. The right ventricle (RV) is the pumping chamber that pumps blood into the pulmonary arteries and the lungs.
PPS can result in high RV pressure, reduced blood flow to one lung, or uneven blood flow within either lung. If left untreated these abnormalities place affected children at risk for abnormal RV function and failure of this pumping chamber which may be seen as decreased ability to do exercise, heart rhythm problems, fainting, or even death.
In the cardiac catheterization laboratory, the investigators treat PPS by dilating the narrowed segments of pulmonary arteries using balloon catheters. Sometimes the investigators also place stents which are mesh tubes that help keep the narrowed vessel open. Some stents suffer from in-growth of tissue into the stents which causes recurrent obstructions inside the stent (i.e. making the opening inside the mesh tube narrow again), so called in-stent stenosis (ISS). This effectively causes recurrent PPS and recurrence of the associated risks listed above.
The purpose of this study is to use a medication that is approved for use in children (for a different purpose) to decrease the amount of cell ingrowth inside the stents (i.e. decrease the problematic in-stent stenosis). The medication is called rapamycin, also known as sirolimus (trade name Rapamune), and has been used safely for many years in children and adults after organ transplantation to prevent rejection of the new organ. It has antiproliferative properties which means that it slows down cell division which the investigators believe cause the recurrent narrowing inside stents. By slowing down the cell division the investigators believe that the stents will stay open instead of becoming narrowed inside again. This medicine is found in many types of stents placed in adults with narrowed arteries around the heart (so called drug-eluding stents) and appear to help keep these blood vessels open after heart attacks (or to prevent heart attacks). Such stents are currently not available for pulmonary arteries; therefore the investigators give the medicine by mouth instead (which has also been used in adults with stents in narrowed arteries around the heart).
Rapamycin is a medicine that can be taken by mouth as a liquid or pill or via a feeding tube. There will still be a need for interventions in the catheterization laboratory but the investigators hope that by taking this medicine some children would need fewer catheterizations in the future. The investigators believe it may help lessen the risk of recurrent in-stent stenosis and the associated problems listed above. Our early experiences with a few patients at BCH who have been treated with rapamycin due to in-stent stenosis in the pulmonary arteries suggest that it may be helpful.
In this study, patients and families who are interested in possibly trying this new approach will be randomized to sirolimus or no sirolimus. The investigators will compare the developement of ISS over time between these groups, in a hope to learn whether oral sirolimus reduces ISS development.
- Conditions
- Peripheral Pulmonary Stenosis, In-stent Stenosis
- Being tested
- Sirolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin, Rapamune
8 weeks oral sirolimus, following drug levels
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Patients randomized to this arm will receive 8 weeks of enteral Rapamycin (sirolimus), with dosage titrated to achieve target blood levels. Receives: Drug: Sirolimus |
| Control | No intervention | No treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in in-stent stenosis
Measured: 6 months
Secondary outcomes (2)
RV pressure
Measured: 6 months
Adverse drug event
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2015 (estimated)
- Study startFeb 2015
- Primary completionApr 2018
- Study completionApr 2018
Why it stopped: Unable to enroll appropriate patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Pulmonary StenosisStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jesse J Esch, Boston Children's Hospital
- Investigators
- Audrey Marshall, MD, Study director, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02365415
- Sponsor's protocol ID
- IRB-P00005257
- Status last verified
- Apr 2018
- First submitted
- 11 Feb 2015
- Last updated
- 5 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic Rapamycin (Sirolimus) to Prevent In-Stent Restenosis Following Pulmonary Artery Stent Placement
- ClinicalTrials.gov ID
- NCT02365415
- Acronym / sponsor ID
- IRB-P00005257
- Conditions
- Peripheral Pulmonary Stenosis, In-stent Stenosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to enroll appropriate patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- Feb 2015 (actual)
- Primary completion
- Apr 2018 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 19 Feb 2015 (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 is a research study to assess whether an oral medication can benefit some patients being treated for peripheral pulmonary stenosis (PPS), which is narrowing of the blood vessels that send blood to the lungs (pulmonary arteries).
In the cardiac catheterization laboratory, the investigators treat PPS by dilating the narrowed segments of pulmonary arteries using balloon catheters. Sometimes the investigators also place stents which are mesh tubes that help keep the narrowed vessel open. Some stents suffer from in-growth of tissue into the stents which causes recurrent obstructions inside the stent (i.e. making the opening inside the mesh tube narrow again), so called in-stent stenosis (ISS).
The purpose of this study is to use a medication that is approved for use in children (for a different purpose) to decrease the amount of cell ingrowth inside the stents (i.e. decrease the problematic in-stent stenosis). The medication is called rapamycin, also known as sirolimus (trade name Rapamune). It has antiproliferative properties which means that it slows down cell division which the investigators believe cause the recurrent narrowing inside stents.
Rapamycin is a medicine that can be taken by mouth as a liquid or pill or via a feeding tube. There will still be a need for interventions in the catheterization laboratory but the investigators hope that by taking this medicine some children would need fewer catheterizations in the future. Our early experiences with a few patients who have been treated with rapamycin due to in-stent stenosis in the pulmonary arteries suggest that it may be helpful.
In this study, patients and families who are interested in possibly trying this new approach will be randomized to sirolimus or no sirolimus. The investigators will compare the developement of ISS over time between these groups, in a hope to learn whether oral sirolimus reduces ISS development.
Detailed description
This is a research study to assess whether an oral medication can benefit some patients being treated for peripheral pulmonary stenosis (PPS). PPS, which can be associated with several different congenital heart diseases, is narrowing of the blood vessels that send blood to the lungs (pulmonary arteries) to pick up oxygen before returning the blood to the heart and the rest of the body. The right ventricle (RV) is the pumping chamber that pumps blood into the pulmonary arteries and the lungs.
PPS can result in high RV pressure, reduced blood flow to one lung, or uneven blood flow within either lung. If left untreated these abnormalities place affected children at risk for abnormal RV function and failure of this pumping chamber which may be seen as decreased ability to do exercise, heart rhythm problems, fainting, or even death.
In the cardiac catheterization laboratory, the investigators treat PPS by dilating the narrowed segments of pulmonary arteries using balloon catheters. Sometimes the investigators also place stents which are mesh tubes that help keep the narrowed vessel open. Some stents suffer from in-growth of tissue into the stents which causes recurrent obstructions inside the stent (i.e. making the opening inside the mesh tube narrow again), so called in-stent stenosis (ISS). This effectively causes recurrent PPS and recurrence of the associated risks listed above.
The purpose of this study is to use a medication that is approved for use in children (for a different purpose) to decrease the amount of cell ingrowth inside the stents (i.e. decrease the problematic in-stent stenosis). The medication is called rapamycin, also known as sirolimus (trade name Rapamune), and has been used safely for many years in children and adults after organ transplantation to prevent rejection of the new organ. It has antiproliferative properties which means that it slows down cell division which the investigators believe cause the recurrent narrowing inside stents. By slowing down the cell division the investigators believe that the stents will stay open instead of becoming narrowed inside again. This medicine is found in many types of stents placed in adults with narrowed arteries around the heart (so called drug-eluding stents) and appear to help keep these blood vessels open after heart attacks (or to prevent heart attacks). Such stents are currently not available for pulmonary arteries; therefore the investigators give the medicine by mouth instead (which has also been used in adults with stents in narrowed arteries around the heart).
Rapamycin is a medicine that can be taken by mouth as a liquid or pill or via a feeding tube. There will still be a need for interventions in the catheterization laboratory but the investigators hope that by taking this medicine some children would need fewer catheterizations in the future. The investigators believe it may help lessen the risk of recurrent in-stent stenosis and the associated problems listed above. Our early experiences with a few patients at BCH who have been treated with rapamycin due to in-stent stenosis in the pulmonary arteries suggest that it may be helpful.
In this study, patients and families who are interested in possibly trying this new approach will be randomized to sirolimus or no sirolimus. The investigators will compare the developement of ISS over time between these groups, in a hope to learn whether oral sirolimus reduces ISS development.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusPatients randomized to this arm will receive 8 weeks of enteral Rapamycin (sirolimus), with dosage titrated to achieve target blood levels. |
| Control | No intervention | –No treatment. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- In-stent stenosis: At least one stent from at least one prior catheterization affected by in-stent stenosis (≥25% stenosis and a diameter narrower or equal to the distal vessel).
- At least one of the following:
- Informed consent of patient and/or parent/guardian
- Agreement to participate in protocol, including follow-up testing
Key exclusion criteria (11 listed)
- Age ≤ 6 months
- Pulmonary artery surgery or transcatheter PA dilations in the past 6 weeks.
- Malignancy (past or present)
- Active infection
- Pregnancy (current or planned within the next 1 year)
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 |
|---|---|---|
| SirolimusAlso: Rapamycin, Rapamune8 weeks oral sirolimus, following drug levels | Drug | Sirolimus |
Primary outcome
Percent change in in-stent stenosis
Time frame: 6 months
2 secondary outcomes
RV pressure
Time frame: 6 months
Adverse drug event
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Individual participant dataSharing planned: No
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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.
Audrey Marshall, MD study director
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus in people with Peripheral Pulmonary Stenosis and In-stent Stenosis, run by Boston Children's Hospital at 1 site 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 7 inclusion and 11 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: withdrawn, as of the sponsor's last update on 5 Apr 2018. 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 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Percent change in in-stent stenosis (time frame: 6 months). 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 5 Apr 2018.