Ischemic Heart Disease, Ischemic Stroke, Peripheral Vascular Disease, Type 2 Diabetes Mellitus
Conditions
Brief summary
This is a randomized double blind 2x2 factorial controlled trial to evaluate efficacy tolerability of low strength Polycap versus two doses of low strength Polycap in patients with stable cardiovascular disease in reducing blood pressure and LDL. To evaluate the tolerability and safety of low dose potassium supplementation compared to placebo in patients with stable cardiovascular disease. Approximately 500 patients are planned to be randomized.
Detailed description
Mean change in blood pressure between those taking 2capsules of the polycap versus one Difference in Rates of early discontinuation between 2 capsules of polycap versus one Rates of reported adverse effects among those taking the polycap
Interventions
DRUGSingle Dose Polycap
Low strength polycap contains Ace inhibitor; betablocker; thiazide diuretic; statin; aspirin
DRUGDouble dose Polycap
2 Capsules of low strength polycap with 30mEq of Potassium
Sponsors
Population Health Research Institute
St. John's Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Individuals 40 years and above, with a seated blood pressure \> 130/80 mm Hg on two consecutive readings (or BP \> 120/80 mm Hg in patients under treatment with 2 or more antihypertensive medication) with one of the following 1. Coronary artery disease; previous myocardial infarction (\>7 days post uncomplicated MI), or 2. Ischemic heart disease with significant ECG changes or a positive stress test, or 3. Stable angina or unstable angina and with documented evidence of multi-vessel (angiography or ECG or CT angiography) coronary artery disease, or 4. PTCA or CABG Surgery \>30 days before informed consent. 5. Cerebrovascular disease; Previous Ischemic stroke or Transient Ischemic Attacks \>30 days before informed consent. 6. High risk diabetes mellitus defined as HbA1C \>7.5%, with microalbuminuria or blood pressure \>140/90 mm Hg. 7. Peripheral artery disease defined as a current or prior history of: physician diagnosed intermittent claudication or vascular surgery for atherosclerotic disease or an ankle/arm systolic blood pressure ratio ≤ 0.90 in either leg at rest, or angiographic or doppler study demonstrating ≥ 70% stenosis in a noncardiac artery. 2. Those who provide informed consent and can comply with medications and follow-up visits.
Exclusion criteria
1. Known hypersensitivity or intolerance to any of the study medications or a clear indication for full doses of beta blockers, RAAS blockers (ACEi, ARBs, Renin inhibitors, etc.), diuretics and statins. 2. History of bleeding or having hemorrhagic stroke anytime in the past or a need for continued anticoagulation therapy. 3. Patients having indication for higher doses of aspirin or needing more than 75mg of clopidogrel daily. 4. Have significant bradycardia (heart rate \<50 beats/min) or second- or third-degree heart block without a pacemaker. 5. Planned cardiac surgery or PTCA or any non-cardiac surgery \<3months of eligibility assessment. 6. Heart transplant recipient. 7. Renal dysfunction defined as serum creatinine \>2 mg/dL and/or serum potassium \>5.0 mEq/L. 8. Patients aged \>70 years, with mild renal dysfunction defined as serum creatinine \>124 µmol/L (1.4 mg/dL) or eGFR \<45 ml/min/1.73 m2. 9. Hepatic dysfunction, SGOT or SGPT \> 3 x ULN. 10. Taking another experimental drug or within 30days of last dose of the experimental drug. 11. Peptic ulcer disease with bleed, or bleeding diathesis. 12. Bronchial asthma or Chronic Obstructive Pulmonary Disease with asthma. 13. Gout, rheumatoid arthritis or other chronic inflammatory disease requiring long-term medications with NSAIDs. 14. Any history of muscular pain, other pathology of the muscles or past history of muscular pain secondary to taking statins or fibrates. 15. Pregnancy or lactating or women of childbearing potential with inadequate contraception. 16. Inability to attend follow up visits (due to significant disability, inadequate address or contact details, subject from a far off place, psychiatric illness etc.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BLOOD PRESSURE LIPIDS | 8 weeks | Amongst patients with cardiovascular disease or type 2 diabetes, the study aims to test the safety and efficacy of giving double dose of polycap versus a single dose of polycap for 8 weeks; efficacy to lower blood pressure and elevated lipids and safety assessed as difference with tolerance to double dose of polycap compared to a single dose. |
| Tolerability of a Double Dose of Half Strength Polycap | 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Blood Pressure Reduction and Lipid Lowering in Type 2 Diabetics | 8 weeks |
Participant flow
Recruitment details
Hospitals in India identified potential consenting eligible subjects with a history of stable cardiovascular disease or high risk for cardiovascular disease and subjected them to an active run in with single dose and then double dose of polycap. Only patients successfully completing the active run in (\>80% compliant) were randomized into the trial
Pre-assignment details
725 Started on Phase 1 run in low dose polycap 645 started on phase 2 run in full dose polycap Only patients who fulfilled \>80% compliance to full dose polycap were randomized to the trial
Participants by arm
| Arm | Count |
|---|---|
| Polycap Single Dose Patients in this arm received single dose of low strength Polycap only Indian Polycap: Polycap contains 5 drugs at half doses Ace inhibitor; betablocker; thiazide diuretic; statin; aspirin | 257 |
| Polycap Double Dose Plus Potassium Patients in this arm received one dose of low strength Polycap with potassium
Indian Polycap: Polycap contains 5 drugs at half doses Ace inhibitor; betablocker; thiazide diuretic; statin; aspirin | 261 |
| Total | 518 |
Baseline characteristics
| Characteristic | Polycap Single Dose | Polycap Double Dose Plus Potassium | Total |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 19.4 | 57.9 years STANDARD_DEVIATION 19.2 | 57.6 years STANDARD_DEVIATION 19.5 |
| Region of Enrollment India | 257 participants | 261 participants | 518 participants |
| Sex: Female, Male Female | 103 Participants | 108 Participants | 211 Participants |
| Sex: Female, Male Male | 154 Participants | 153 Participants | 307 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 257 | 4 / 261 |
| serious Total, serious adverse events | 9 / 257 | 1 / 261 |
Outcome results
Primary
BLOOD PRESSURE LIPIDS
Amongst patients with cardiovascular disease or type 2 diabetes, the study aims to test the safety and efficacy of giving double dose of polycap versus a single dose of polycap for 8 weeks; efficacy to lower blood pressure and elevated lipids and safety assessed as difference with tolerance to double dose of polycap compared to a single dose.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Two Doses of Low Strength Polycap | BLOOD PRESSURE LIPIDS | 126.6 mmHG |
| One Dose of Low Srength Polycap | BLOOD PRESSURE LIPIDS | 129.9 mmHG |
Primary
Tolerability of a Double Dose of Half Strength Polycap
Time frame: 8 weeks
Secondary
Blood Pressure Reduction and Lipid Lowering in Type 2 Diabetics
Time frame: 8 weeks