Valsartan for Suppression of Plaque Volume and Restenosis After Drug-Eluting Stent

NCT ID: NCT00589732

Last Updated: 2012-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-12-31

Brief Summary

To evaluate that angiotensin-converting enzyme (ACE) inhibitors and angiotensin-converting enzyme receptor blockers (ARBs) reduce the risk of restenosis after DES implantation.

Detailed Description

Stimulation of the angiotensin II type 1 (AT1) receptors after arterial injury promotes vascular smooth muscle cell (VSMC) migration, proliferation, and extracellular matrix production, leading to the hope that blockade of this receptor by angiotensin-converting enzyme inhibitors (ACEI) or specific (AT1) receptor antagonists (ARBs) might reduce intimal hyperplasia. However, despite confirmatory evidence in several animal models of restenosis, the large scale MERCATOR and MARCATOR trials of cilazapril with balloon angioplasty failed to show benefit. In 1999, Kondo reported the results of a randomized pilot trial of 100 patients who received Palmaz-Schatz stents and were randomized to receive the ACE inhibitor quinapril or placebo. The volume of neointimal hyperplasia assessed by IVUS was significantly less quinapril than the control group (18 ± 0.6 mm3 vs. 25 ± 0.6 mm3; p < 0.05). The quinapril group's restenosis rate was 16%, with the quinapril benefit being observed only in patients with the D/D and I/D genotypes. Also, other study reported on a consecutively treated cohort of 1,598 stented patients, noting that ACE inhibitor usage at the time and after stenting reduced the risk of subsequent revascularization dramatically (adjusted odds ratio, 0.46; p = 0.001). In the ValPREST trial which is a single-center randomized trial of patients receiving stents for type B2/C lesions, comparing valsartan (and ARV) 80 mgs daily with open treatment, patients randomized to valsartan had a 19% incidence of restenosis compared with 39% in the open treatment arm (p = 0.005).

Recently, several randomized studies were conducted to compare the safety and efficacy of the two leading drug-eluting stent (DES). However, data on the association of ARBs for suppression of neointimal hyperplasia are limited in the DES era. Therefore, a pivotal randomized study is warranted.

Conditions

Coronary Artery Disease

Keywords

stents; angiotensin-converting enzyme

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Valsartan treatment gorup

Valsartan 160mg per day group

Group Type: EXPERIMENTAL

Valsartan

Intervention Type: DRUG

Valsartan 160mg per day

No Valsartan treatment group

No valsartan treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Valsartan

Valsartan 160mg per day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Clinical 1) Patients with angina and documented ischemia or patients with documented silent ischemia 2) Patients who are eligible for intracoronary stenting 3) Age >18 years, <75 ages 4) Preserved left ventricular ejection fraction (>40%) 5) Written informed consent to the study protocol 6) Patients with hemodynamic stability and appropriate blood pressure, which were suitable for administration of valsartan 160mg

2. Angiographic: Patients who have

1) Significant ischemic narrowing (target vessel)

1. De novo coronary lesion (no restriction of lesion length)

2. Percent diameter stenosis ≥50% by visual estimate

3. Reference vessel size ≥2.5 mm by visual estimation

4. Lesions suitable for stenting

And/Or

2) Non-significant non-ischemic intermediate narrowing (non-target vessel)

1. Percent diameter stenosis 20%~50% by visual estimate

2. No objective evidence of ischemia

Exclusion Criteria

1. Patients received a Angiotensin converting enzyme inhibitor (ACE-I) or ACE-receptor blockers (ARBs) in the previous week prior to enrollment

2. History of bleeding diathesis or coagulopathy

3. Pregnant

4. Known hypersensitivity or contra-indication to contrast agent and heparin

5. Limited life-expectancy (less than 1 year)

6. Acute ST-elevation myocardial within 1 week

7. Characteristics of lesion 1) Left main disease 2) In-stent restenosis 3) Graft vessels

8. Hematological disease (Neutropenia <3000/mm3, Thrombocytopenia <100,000/mm3)

9. Hepatic dysfunction, liver enzyme (ALT and AST) elevation >3 times normal

10. Renal dysfunction, creatinine >2.0mg/dL

11. Contraindication to aspirin and clopidogrel

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Seung-Jung Park

OTHER

Sponsor Role: lead

Responsible Party

Seung-Jung Park

M.D., Ph.D.,Professor of Medicine Asan Medical Center, University of Ulsan, College of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Seung-Jung Park, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine

Locations

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

St. Mary's Catholic Medical Center

Seoul, , South Korea

Yonsei University Medical Center

Seoul, , South Korea

Ajou University Hospital

Suwon, , South Korea

Countries

South Korea

Other Identifiers

2006-0077

Identifier Type: -

Identifier Source: org_study_id