Angiotensin Converting Enzyme (ACE) Inhibition and Peripheral Arterial Disease
Information source: Bayside Health
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Peripheral Arterial Disease
Intervention: Ramipril or matching placebo (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Bayside Health Official(s) and/or principal investigator(s):
Bronwyn A Kingwell, PhD, Principal Investigator, Affiliation: Baker Heart Research Institute
Overall contact:
Anna A Ahimastos, PhD, Phone: +61 3 9076 2356, Email: A.Ahimastos@alfred.org.au
Summary
Leg pain caused by peripheral arterial disease (PAD) can severely impede walking ability.
Our preliminary findings indicate that the drug ramipril is much more effective in improving
walking ability than current therapies. To be accepted as a new treatment for PAD these
findings require validation in a much larger clinical trial. We propose to examine the
effects of ramipril therapy for 6 months in a randomized, controlled trial of patients with
PAD. If positive, this study will identify ramipril as a potential new therapy for PAD.
Clinical Details
Official title: ACE Inhibition; A Potential New Therapy for Peripheral Arterial Disease
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: walking time
Secondary outcome: walking impairment questionnaire
Detailed description:
This proposal extends our novel finding that the angiotensin-converting enzyme (ACE)
inhibitor, ramipril markedly improves walking ability in patients with peripheral arterial
disease (PAD), by conducting a larger clinical trial including a broader cross-section of
PAD patients.
Hypothesis:
That ramipril therapy for 24 weeks will result in clinically significant increases in both
pain-free and maximum walking time and improve quality of life in patients with PAD.
Background Synopsis:
Peripheral arterial disease is a common disorder, with 12% of adults over 50 having an
ankle-brachial index (ABI) diagnostic of PAD (<0. 9). Approximately one third of these
patients experience intermittent claudication during walking, limiting the ability of these
older individuals to participate in normal activities. The aim of PAD treatment is to
improve walking distance and quality of life in those with intermittent claudication, and to
decrease long term cardiovascular morbidity and mortality. However, the range of medical
treatments to improve walking distance in these patients is limited. Our pilot study
demonstrates that treatment of PAD patients, with infra-inguinal disease and without
diabetes with ramipril for 24 weeks, markedly improves waking ability. Relative to placebo,
ramipril increased mean treadmill-assessed pain-free waking time by 227s (160%, p<0. 001) and
mean maximum walking time by 451s (240%, p<0. 001). Assuming a constant speed of 0. 89 m/s
(3. 2 km/hr), this corresponds to a clinically significant increase in walking distance of
401m (95% CI 330m to 480m) which would impact appreciably on daily functional capacity. The
magnitude of this effect is significantly greater than that reported for conventional
medical therapies and provides worthwhile clinical benefit.
Research Plan Synopsis:
The dramatic findings of our pilot study clearly warrant verification in a larger clinical
trial including diabetic patients and those with aorto-iliac disease as well as
infra-inguinal disease. The current proposal is to expand our pilot study into a large trial
with broad inclusion criteria. We propose to include patients with diabetes mellitus not
currently medicated with ACE inhibitors. 264 PAD patients will be randomised to either
ramipril (10mg once daily) or matching placebo for 24 weeks in a randomised, double-blind
placebo controlled trial. All patients will undergo a treadmill exercise test to determine
pain free and maximum walking times, ABI measurements and Duplex scanning to determine
stenosis severity, both at baseline and following 6 months of ramipril therapy. Functional
capacity in a daily life setting, will be assessed using standardised questionnaires
(Walking Impairment Questionnaire and Quality of Life Questionnaire).
Outcomes and Significance:
If positive this trial will validate our pilot findings that the ACE inhibitor ramipril is
an efficacious new therapy for the treatment of patients with claudication resulting from
PAD. Given the escalating prevalence of PAD, this work has the potential for widespread
impact.
Eligibility
Minimum age: 40 Years.
Maximum age: 85 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Ankle brachial index of <0. 9 in at least one leg
- History of intermittent claudication (unilateral or bilateral)
- A stable medication regimen for at least 6 months
Exclusion Criteria:
- Limiting coronary artery disease
- Renal failure (serum creatinine > 0. 20 mmol/L)
- Current treatment or treatment within the previous 6 months with ACE inhibitors or
angiotensin II receptor antagonists
Locations and Contacts
Anna A Ahimastos, PhD, Phone: +61 3 9076 2356, Email: A.Ahimastos@alfred.org.au
Baker Heart Research Institute, Melbourne, Victoria 8008, Australia; Recruiting
Anna A Ahimastos, PhD, Phone: +61 3 9076 2356, Email: A.Ahimastos@alfred.org.au
Additional Information
Related publications: Ahimastos AA, Lawler A, Reid CM, Blombery PA, Kingwell BA. Brief communication: ramipril markedly improves walking ability in patients with peripheral arterial disease: a randomized trial. Ann Intern Med. 2006 May 2;144(9):660-4. Summary for patients in: Ann Intern Med. 2006 May 2;144(9):I24.
Starting date: January 2008
Ending date: December 2011
Last updated: May 20, 2008
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