Oral Sirolimus for In-Stent Restenosis

Study Overview
=================
Brief Summary
-----------------
Despite recent advances in interventional cardiology including the success of drug-eluting stents in de-novo coronary lesions, the treatment of in-stent restenosis remains a challenging clinical issue. Given the efficacy of the systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with two different loading regimens for the prevention of recurrent restenosis in patients with in-stent restenosis.

Detailed Description
-----------------
Three-hundred symptomatic patients with in-stent restenotic lesions were randomly assigned to one of three treatment arms: placebo, usual dose or high dose sirolimus. Patients received a cumulative loading dose of 0, 8 or 24 mg of sirolimus two days prior to and the day of repeat intervention followed by maintenance therapy of 2 mg/day for 7 days. Angiographic restenosis at 6-months angiography was the primary end point of the study.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Trial Investigating the Impact of Oral Sirolimus on Restenosis Prevention in Patients With In-Stent Restenosis.

Conditions
-----------------
Coronary Restenosis

Intervention / Treatment
-----------------
* Drug: Sirolimus
* Drug: Sirolimus
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with angina pectoris or exercise-induced ischemia in the presence of angiographically significant in-stent-restenosis in native coronary arteries. Exclusion Criteria: Patients with acute coronary syndromes or with severe infectious diseases the presence of severe kidney failure (serum creatinine > 2.2 mg/dl) contraindications to sirolimus

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>cumulative loading dose of 8 mg of sirolimus two days prior to and the day of repeat intervention followed by maintenance therapy of 2 mg/day for 7 days | Drug: Sirolimus<br>* cumulative loading dose of 8 mg of oral sirolimus two days prior to and the day of repeat intervention followed by maintenance therapy of 2 mg/day for 7 days<br>* Other names: Rapamune;|
| Active Comparator: 2<br>cumulative loading dose of 24 mg of oral sirolimus two days prior to and the day of repeat intervention followed by maintenance therapy of 2 mg/day for 7 days | Drug: Sirolimus<br>* cumulative loading dose of 24 mg of oral sirolimus two days prior to and the day of repeat intervention followed by maintenance therapy of 2 mg/day for 7 days<br>* Other names: Rapamune;|
| Placebo Comparator: 3<br>oral placebo | Drug: Placebo<br>* Placebo oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angiographic restenosis |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The combined incidence of death and myocardial infarction as well as target vessel revascularization |  | one year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
in-stent restenosis, stents, sirolimus