Clinical trial NCT01037530: Clinical and Cost Effectiveness of ACE Inhibitor, Ramipril, in Intermittent Claudicants
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Intermittent Claudicants
Keywords: ACE inhibitors
Intermittent claudication
Ramipril
Lead sponsor: University of Hull
Sponsor class: OTHER
First posted: 2009-12-23
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: 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.
timeFrame: 0,2,6,24 weeks
Secondary outcomes:
measure: 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)
timeFrame: 0,2,6,24 weeks
measure: Quality of life: a) Generic - measured using the SF36, SF8 and EuroQol (EQ5D) instruments b) Disease specific - measured using the VascuQol
timeFrame: 0,2,6,24 weeks
measure: 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)
timeFrame: 0,2,6,24 weeks
measure: 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)
timeFrame: 0,2,6,24 weeks
measure: 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
timeFrame: 0,2,6,24 weeks
measure: Health economics (cost effectiveness / utility)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Hospitals
state: Yorkshire
Study officials:
affiliation: University of Hull
name: Ian Chetter, MD, FRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.