Clinical and Cost Effectiveness of ACE Inhibitor, Ramipril, in Intermittent Claudicants

A Double Blind, Randomised, Placebo Controlled Trial to Study the Clinical and Cost Effectiveness of the Angiotensin Converting Enzyme Inhibitor, Ramipril, in Intermittent Claudicants

The investigators are conducting a randomised controlled trial to investigate the clinical and cost effectiveness of Ramipril which is an anti-hypertensive medication in patients with intermittent claudication. The investigators aim to recruit 78 participants in total. The investigators will randomise the 78 participants into two groups: Ramipril group with 39 participants and Placebo group with 39 participants. The investigators will measure Ramipril's effect on walking by doing a simple treadmill test and measuring the maximum walking distance the participant can walk. The investigators also want to examine Ramipril's effect on arterial function, cardiovascular prognosis, quality of life and cost effectiveness.

Study Overview

• Status: Completed
• Conditions: Intermittent Claudicants
• Intervention / Treatment: Drug: Ramipril

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Yorkshire
    • Hull, Yorkshire, United Kingdom, HU3 2JZ
      • Hull and East Yorkshire Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with unilateral or bilateral intermittent leg claudication which was stable for the last 6 months.
• Patients with ABPI < 0.9 at rest at least in one leg.
• BP ≤ 160/90 and a stable medication regimen for the last 6 months.
• Able to give informed consent
• Able to comply with study protocol

Exclusion Criteria:

• Documented bilateral renal artery stenosis
• Unlikely to be compliant with medication or follow up as determined by the recruiting institution.
• Pregnancy
• Patients with critical limb ischemia (This includes patients with ischaemic rest pain and ulceration > 2 weeks and/or a resting ankle pressure < 50mmHg- Grades II and III according to Rutherford et al 1997.[56].
• Patients who had a recent (less than 3 months) angioplasty or bypass surgery
• Patients who are unable to perform a treadmill test due to a limiting heart, respiratory or arthritic disease
• History of angioneurotic oedema
• Currently taking ACE inhibitor or Angiotensin receptor blocker
• Contraindication to ACE inhibitor
• History of ACE inhibitor intolerance
• A creatinine rise of > 30% from baseline and/or Potassium > 5.9 mmol/l
• Unwillingness to participate.
• Level 1 evidence for ACE inhibitor treatment, including:

• Documented heart failure, left ventricular dysfunction or ejection fraction <35% on previous echocardiography

  • Uncontrolled hypertension, BP > 160mmHg systolic or 100mmHg diastolic on 3 separate readings measured after 10 minutes rest on 2 separate occasions
  • Recent (< 3months) myocardial infarction or stroke
  • Chronic renal impairment (serum creatinine > 250 micromol/l)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ramipril	Drug: Ramipril; 5 mg/day for 2 weeks then 10 mg/day for 22 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome measure for this trial is the Maximum Walking Distance (MWD). Treadmill exercise test will be used to estimate the maximum distance the participant can walk at a speed of 2.5 km/h with a 10 degree incline.	0,2,6,24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Other clinical indicators of lower limb ischaemia: a) Patient Reported Walking Distance (PRWD) b) Treadmill Intermittent Claudication Distance (ICD) c) Ankle Brachial Pressure Index at rest (ABPI- r) and following treadmill testing (ABPI - t)	0,2,6,24 weeks
Quality of life: a) Generic - measured using the SF36, SF8 and EuroQol (EQ5D) instruments b) Disease specific - measured using the VascuQol	0,2,6,24 weeks
Cardiovascular prognosis using: a) Framingham, PROCAM, QRISK and Manchester charts scoring systems b) B-type Natriuretic Peptide (BNP) and N- terminal prohormone BNP (NT-proBNP) and a Lipid profile ( LDL, HDL, Total Cholesterol, Triglycerides)	0,2,6,24 weeks
Markers of endothelial function and ischaemia reperfusion a) IL6 b) soluble Intercellular Adhesion Molecule-1 (sICAM -1) c) sE selectin d) Urine Albumin Creatinine Ratio ( UACR)	0,2,6,24 weeks
Arterial effects: a) Arterial stiffness by measuring the Pulse Wave Velocity and assessing the effects on the extracellular matrix by measuring Metalloproteinases (MMPs) and Tissue Inhibitor Metalloproteinases (TIMPs). b) Flow mediated vasodilatation	0,2,6,24 weeks
Health economics (cost effectiveness / utility)	24 weeks

Collaborators and Investigators

• Sponsor: Daniel Carradice
• Investigators: Principal Investigator: Ian Chetter, MD, FRCS, University of Hull

Publications and helpful links

General Publications

• Shahin Y, Cockcroft JR, Chetter IC. Randomized clinical trial of angiotensin-converting enzyme inhibitor, ramipril, in patients with intermittent claudication. Br J Surg. 2013 Aug;100(9):1154-63. doi: 10.1002/bjs.9198.

Helpful Links

• Related publications

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): December 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: December 22, 2009
• First Submitted That Met QC Criteria: December 22, 2009
• First Posted (ESTIMATE): December 23, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 19, 2014
• Last Update Submitted That Met QC Criteria: December 18, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: ACE inhibitors; Ramipril; Intermittent claudication
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Ramipril
• Other Study ID Numbers: 05102009; 2009-016600-23 (REGISTRY: European Clinical Trials Database (EudraCT))