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

NCT02365415 | Withdrawn Phase 2 DMC

• 1 other identifier: IRB-P00005257
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Peripheral Pulmonary Stenosis; In-stent Stenosis

Outcome Measures

Primary Outcomes (1)

• Percent change in in-stent stenosis

  6 months

Secondary Outcomes (2)

• RV pressure

  6 months

• Adverse drug event

  6 months

Study Arms (2)

Sirolimus

EXPERIMENTAL

Patients randomized to this arm will receive 8 weeks of enteral Rapamycin (sirolimus), with dosage titrated to achieve target blood levels.

Drug: Sirolimus

Control

NO INTERVENTION

No treatment.

Interventions

Sirolimus DRUG

8 weeks oral sirolimus, following drug levels

Also known as: Rapamycin, Rapamune

Sirolimus

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Audrey Marshall, MD

  Boston Children's Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Cardiologist, Instructor in Pediatrics

Study Record Dates

• First Submitted: February 11, 2015
• First Posted: February 19, 2015
• Study Start: February 1, 2015
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: April 5, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)