Clinical trial NCT00589732: Valsartan for Suppression of Plaque Volume and Restenosis After Drug-Eluting Stent
Official title: Valsartan for SUPpression of Plaque Volume and Restenosis After Drug-Eluting Stent (The VAL-SUPPRESS TRial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: stents
angiotensin-converting enzyme
Lead sponsor: CardioVascular Research Foundation, Korea
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2008-01-10
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Angiographic in-stent late-loss (target vessel)
timeFrame: at 8-month follow-up.
Secondary outcomes:
measure: 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
timeFrame: 30 days
measure: Composite of Major cardiac adverse events including death, Q-MI, Non Q-MI, and target lesion or vessel revascularization
timeFrame: 9 months
measure: Each component of MACE
timeFrame: 3 days in average
measure: Each component of MACE
timeFrame: 30 days
measure: Each component of MACE
timeFrame: 9 months
measure: In-stent and in-segment restenosis rate
timeFrame: 8 months
measure: In-segment late loss
timeFrame: 8 months
measure: Percent atheroma volume of 10mm length by IVUS examination (non-target vessel) in IVUS-substudy
timeFrame: 8 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: St. Mary's Catholic Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Medical Center
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
Study officials:
affiliation: Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine
name: Seung-Jung Park, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: