Systemic Rapamycin (Sirolimus) to Prevent In-Stent Restenosis Following Pulmonary Artery Stent Placement

April 3, 2018 updated by: Jesse J Esch, Boston Children's Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sirolimus
Patients randomized to this arm will receive 8 weeks of enteral Rapamycin (sirolimus), with dosage titrated to achieve target blood levels.
Drug: Sirolimus
8 weeks oral sirolimus, following drug levels
Other Names:
  • Rapamycin, Rapamune
No Intervention: Control
No treatment.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percent change in in-stent stenosis
Time Frame: 6 months
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
RV pressure
Time Frame: 6 months
6 months
Adverse drug event
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boston Children's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Audrey Marshall, MD, Boston Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 11, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 18, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 19, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 5, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB-P00005257

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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