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

Coronary Artery Disease Clinical Trial

— VAL-SUPPRES  

Official title:

Valsartan for SUPpression of Plaque Volume and Restenosis After Drug-Eluting Stent (The VAL-SUPPRESS TRial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00589732
• Other study ID #: 2006-0077
• Status: Completed
• Phase: Phase 4
• First received: December 31, 2007
• Last updated: August 7, 2012
• Start date: September 2006
• Est. completion date: December 2009

Study information

• Verified date: August 2012
• Source: CardioVascular Research Foundation, Korea
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Valsartan
Valsartan 160mg per day

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	St. Mary's Catholic Medical Center	Seoul
Korea, Republic of	Yonsei University Medical Center	Seoul
Korea, Republic of	Ajou University Hospital	Suwon

Sponsors (2)

Lead Sponsor	Collaborator
Seung-Jung Park	Novartis

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Angiographic in-stent late-loss (target vessel)		at 8-month follow-up.	No
Secondary	Composite of Major cardiac adverse events including death, Q-MI, Non Q-MI, and target lesion or vessel revascularization -Delta change in percent atheroma area and volume		30 days	Yes
Secondary	Composite of Major cardiac adverse events including death, Q-MI, Non Q-MI, and target lesion or vessel revascularization		9 months	Yes
Secondary	Each component of MACE	3 day hospitalization is normal for index procedure and outcome needs to be measured at discharge.	3 days in average	Yes
Secondary	Each component of MACE		30 days	Yes
Secondary	Each component of MACE		9 months	Yes
Secondary	In-stent and in-segment restenosis rate		8 months	No
Secondary	In-segment late loss		8 months	No
Secondary	Percent atheroma volume of 10mm length by IVUS examination (non-target vessel) in IVUS-substudy		8 months	No