Intermittent Claudicants
Conditions
Keywords
ACE inhibitors, Intermittent claudication, Ramipril
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.
Interventions
DRUGRamipril
5 mg/day for 2 weeks then 10 mg/day for 22 weeks
Sponsors
University of Hull
Hull University Teaching Hospitals NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Walking Distance (MWD). | Baseline | 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 |
Secondary
| 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) | Baseline |
| 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 |
| Health Economics (Cost Effectiveness / Utility) | 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 |
| 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 |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ramipril Ramipril: 5 mg/day for 2 weeks then 10 mg/day for 22 weeks | 14 |
| Placebo Ramipril: 5 mg/day for 2 weeks then 10 mg/day for 22 weeks | 19 |
| Total | 33 |
Baseline characteristics
| Characteristic | Ramipril | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.4 Years STANDARD_DEVIATION 8.2 | 64.7 Years STANDARD_DEVIATION 7.7 | 64.55 Years STANDARD_DEVIATION 7.82 |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 11 Participants | 14 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 14 | 0 / 19 |
| serious Total, serious adverse events | 0 / 14 | 0 / 19 |
Outcome results
Primary
Maximum Walking Distance (MWD).
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
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramipril | Maximum Walking Distance (MWD). | 137 Metres |
| Placebo | Maximum Walking Distance (MWD). | 143 Metres |
Secondary
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
Secondary
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
Secondary
Health Economics (Cost Effectiveness / Utility)
Time frame: 24 weeks
Secondary
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
Secondary
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: Baseline
Secondary
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