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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01037530
Recruitment Status : Completed
First Posted : December 23, 2009
Last Update Posted : December 19, 2014
Information provided by (Responsible Party):
Daniel Carradice, University of Hull

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Intermittent Claudicants Drug: Ramipril Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind, Randomised, Placebo Controlled Trial to Study the Clinical and Cost Effectiveness of the Angiotensin Converting Enzyme Inhibitor, Ramipril, in Intermittent Claudicants
Study Start Date : December 2010
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Ramipril

Arm Intervention/treatment
Experimental: Ramipril Drug: Ramipril
5 mg/day for 2 weeks then 10 mg/day for 22 weeks

Primary Outcome Measures :
  1. 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. [ Time Frame: 0,2,6,24 weeks ]

Secondary Outcome Measures :
  1. 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) [ Time Frame: 0,2,6,24 weeks ]
  2. Quality of life: a) Generic - measured using the SF36, SF8 and EuroQol (EQ5D) instruments b) Disease specific - measured using the VascuQol [ Time Frame: 0,2,6,24 weeks ]
  3. 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) [ Time Frame: 0,2,6,24 weeks ]
  4. 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) [ Time Frame: 0,2,6,24 weeks ]
  5. 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 [ Time Frame: 0,2,6,24 weeks ]
  6. Health economics (cost effectiveness / utility) [ Time Frame: 24 weeks ]

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01037530

United Kingdom
Hull and East Yorkshire Hospitals
Hull, Yorkshire, United Kingdom, HU3 2JZ
Sponsors and Collaborators
Daniel Carradice
Principal Investigator: Ian Chetter, MD, FRCS University of Hull

Additional Information:
Publications of Results:
Responsible Party: Daniel Carradice, Clinical Lecturer, University of Hull Identifier: NCT01037530     History of Changes
Other Study ID Numbers: 05102009
2009-016600-23 ( Registry Identifier: European Clinical Trials Database (EudraCT) )
First Posted: December 23, 2009    Key Record Dates
Last Update Posted: December 19, 2014
Last Verified: December 2014

Keywords provided by Daniel Carradice, University of Hull:
ACE inhibitors
Intermittent claudication

Additional relevant MeSH terms:
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents