Valsartan for Suppression of Plaque Volume and Restenosis After Drug-Eluting Stent (VAL-SUPPRES)

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Seung-Jung Park, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier:
NCT00589732
First received: December 31, 2007
Last updated: August 7, 2012
Last verified: August 2012
  Purpose

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


Condition Intervention Phase
Coronary Artery Disease
Drug: Valsartan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Valsartan for SUPpression of Plaque Volume and Restenosis After Drug-Eluting Stent (The VAL-SUPPRESS TRial)

Resource links provided by NLM:


Further study details as provided by CardioVascular Research Foundation, Korea:

Primary Outcome Measures:
  • Angiographic in-stent late-loss (target vessel) [ Time Frame: at 8-month follow-up. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Composite of Major cardiac adverse events including death, Q-MI, Non Q-MI, and target lesion or vessel revascularization [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • Each component of MACE [ Time Frame: 3 days in average ] [ Designated as safety issue: Yes ]
    3 day hospitalization is normal for index procedure and outcome needs to be measured at discharge.

  • Each component of MACE [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Each component of MACE [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • In-stent and in-segment restenosis rate [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • In-segment late loss [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Percent atheroma volume of 10mm length by IVUS examination (non-target vessel) in IVUS-substudy [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Enrollment: 220
Study Start Date: September 2006
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Valsartan treatment gorup
Valsartan 160mg per day group
Drug: Valsartan
Valsartan 160mg per day
No Intervention: No Valsartan treatment group
No valsartan treatment

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589732

Locations
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
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, Korea, Republic of
Sponsors and Collaborators
Seung-Jung Park
Novartis
Investigators
Principal Investigator: Seung-Jung Park, MD, PhD Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine
  More Information

No publications provided

Responsible Party: Seung-Jung Park, M.D., Ph.D.,Professor of Medicine Asan Medical Center, University of Ulsan, College of Medicine, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier: NCT00589732     History of Changes
Other Study ID Numbers: 2006-0077
Study First Received: December 31, 2007
Last Updated: August 7, 2012
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by CardioVascular Research Foundation, Korea:
stents
angiotensin-converting enzyme

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Valsartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014