NCT00699452

Brief Summary

The present study defines a blinded, randomized, placebo-controlled, prospective study, the aim of which is to determine the influence of effective treatment with Type 1 angiotensin II (Ang II) receptor (AT-1R) antagonist, using candesartan (target dose 16 mg) on stenotic aortic valves. The investigators will specifically quantify whether candesartan attenuates the key pathogenic mechanisms of aortic valve stenosis, namely inflammation, fibrosis, elastin degradation, calcification, and neovascularization.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
120

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started May 2009

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 16, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 18, 2008

Completed
11 months until next milestone

Study Start

First participant enrolled

May 1, 2009

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
Last Updated

May 19, 2009

Status Verified

May 1, 2009

Enrollment Period

3.6 years

First QC Date

June 16, 2008

Last Update Submit

May 18, 2009

Conditions

Aortic Valve Stenosis

Keywords

aortic stenosisvalvecandesartan

Outcome Measures

Primary Outcomes (1)

  • The degree of inflammation in stenotic aortic valves

    3-5 months

Secondary Outcomes (1)

  • The degree of calcification, lipid accumulation, and fibrosis in stenotic aortic valves

    3-5 months

Study Arms (2)

1

ACTIVE COMPARATOR

Candesartan 8 mg/d for two weeks, then 16 mg/d until valve replacement surgery (approximately 3 months)

Drug: candesartan

2

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

candesartanDRUG

Candesartan 8 mg/d for two weeks, then 16 mg/d until valve replacement surgery (approximately 3 months)

Also known as: Atacand
1
placeboDRUG

placebo

2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • consecutive patients with clinically significant, symptomatic aortic stenosis referred to the Helsinki University Central Hospital for consideration of valve replacement surgery.

You may not qualify if:

  • Individuals with past myocardial infarction, more than mild mitral valve disease, or previous cardiac surgery will be excluded.
  • Patients with heart failure who need urgent surgery or those with hypotension (systolic blood pressure below 110 mm Hg) will be excluded.
  • Patients already taking ACE inhibitors or AT-1R antagonists will be excluded from the study population.
  • Complicated diabetes
  • Primary cardiomyopathy
  • Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception or have a positive serum pregnancy test
  • History of malignancy (unless a documented disease free period exceeding 5-years is present) with the exception of basal cell or squamous cell carcinoma of the skin. Women with a history of cervical dysplasia would be permitted to enter the study provided they had 3 consecutive clear Papanicolaou (Pap) smears
  • Hypothyroidism (TSH 1.5xULN)
  • History of alcohol or drug abuse within the last 5 years (this may affect compliance)
  • Unexplained creatine kinase (CK 3xULN) (To protect patient safety)
  • Serum creatinine \>176 umol/L (2.0mg/dL)
  • Participation in another investigational drug study less than 4 weeks before enrolment in the study, or according to subjects local ethics committee requirements where a larger period is stipulated (to avoid potential misinterpretation of overlapping adverse events)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Division of Cardiology, Helsinki University Central Hospital

Helsinki, 00029, Finland

RECRUITING

Related Publications (1)

  • Helske-Suihko S, Laine M, Lommi J, Kaartinen M, Werkkala K, Kovanen PT, Kupari M. Is blockade of the Renin-Angiotensin system able to reverse the structural and functional remodeling of the left ventricle in severe aortic stenosis? J Cardiovasc Pharmacol. 2015 Mar;65(3):233-40. doi: 10.1097/FJC.0000000000000182.

    PMID: 25469804DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

candesartancandesartan cilexetil

Condition Hierarchy (Ancestors)

Aortic Valve DiseaseHeart Valve DiseasesHeart DiseasesCardiovascular DiseasesVentricular Outflow Obstruction

Study Officials

  • Markku Kupari, MD, PhD

    Division of Cardiology, Helsinki University Central Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Markku Kupari, MD, PhD

CONTACT

358-9-4717-2441markku.kupari@hus.fi

Satu Helske, MD, PhD

CONTACT

358-9-681-411satu.helske@wri.fi

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

June 16, 2008

First Posted

June 18, 2008

Study Start

May 1, 2009

Primary Completion

December 1, 2012

Study Completion

December 1, 2014

Last Updated

May 19, 2009

Record last verified: 2009-05

Locations

FI(1)