Primary Hypertension
Conditions
Brief summary
Hypertension is a leading cause of morbidity and mortality globally. Although multiple drugs are frequently used to treat it, in the South Asian context, evidence is lacking on best drug combinations. This trial aims to compare efficacy of three single-pill combinations of two anti-hypertensive agents on 24-hour ambulatory systolic blood pressure among 1968 individuals with hypertension. The trial is a single-blind randomized controlled trial spread across 37 hospitals in India. Single Pill combinations (SPCs): 1) Amlodipine + Perindopril, 2) Perindopril + Indapamide, 3) Amlodipine + Indapamide
Detailed description
This is a multi-centre, individual randomized single-blind, parallel group, three-armed superiority trial to compare the efficacy of three different single-pill combinations of antihypertensive therapies (Amlodipine/Perindopril, Perindopril/Indapamide, and Amlodipine/Indapamide)on 24-hour ambulatory BP levels in Indians.
Interventions
DRUGAmlodipine + Perindopril
Single pill combination of dual antihypertensive agent
DRUGPerindopril + Indapamide
Single pill combination of dual antihypertensive agent
DRUGAmlodipine + Indapamide
Single pill combination of dual antihypertensive agent
Sponsors
All India Institute of Medical Sciences
Imperial College London
Centre for Chronic Disease Control, India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. Age 30-79 years AND 2. Sitting clinic values\* of SBP ≥140 mmHg and \<160 mmHg on one antihypertensive agent OR 3. Sitting clinic values\* of SBP ≥150 mmHg and \<180 mmHg on no antihypertensive treatment \* Mean of the last 2 of 3 readings.
Exclusion criteria
1. Congestive heart failure (clinically defined). 2. Patients with a history of intolerance to any of the study medications for example angioedema or dry cough with Angiotensin-converting enzyme inhibitors. 3. Serum creatinine levels greater than 132.6µmol/l (1.5mg/dl) 4. 4\. History of coronary heart disease (i.e., chronic stable angina, myocardial infarction or acute coronary syndrome). 5. History of a stroke or other cerebrovascular accident (i.e. transient ischaemic attack or reversible ischaemic neurological deficit). 6. Severe hepatic impairment 7. Treatment with agents causing torsades de pointes 8. Lactation 9. Contraindications to any of the investigational medicinal products as per the summaries product characteristics of drugs studied 10. Known or suspected secondary hypertension. 11. Any other concomitant illness, physical or mental impairment that could interfere with the effective conduct of the study. 12. Pregnancy or those of child-bearing age who are not taking reliable contraception. 13. History of Gout. 14. Serum potassium \< 3.5mmol/L at screening. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour ambulatory systolic Blood Pressure | Change in between baseline and 6 month Ambulatory Systolic Blood Pressure | To determine which of three single pill combinations of two anti-hypertensive agents is most effective in reducing 24-hour ambulatory systolic BP (ASBP) in Indian patients with hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinic Blood Pressure | Comparison of Clinic blood pressure measured at baseline 2 month , 4 month and 6 month | To determine which of three single pill combinations of two antihypertensive agents is most effective in reducing Clinic SBP and diastolic blood pressure (DBP) at two, four and six months adjusted for baseline values |
| Daytime and nighttime Blood Pressure | Change in between baseline and 6 month ASBP and ADBP | To determine which of three single pill combinations of two antihypertensive agents is most effective in reducing Daytime and nighttime blood pressure (BP) a t six months adjusted for baseline values |
| BP variability measured by ABPM and within-visit clinic BPs | Fluctuations in Ambulatory blood pressures as measured at baseline and 6 month and fluctuation in Clinic BP as measured at baseline, 2 month, 4 month and 6 month | To determine which of three single pill combinations of two antihypertensive agents is most effective in reducing 3.2.4. BP variability measured by ASBP and within-visit clinic BP |
| Proportion of patients who achieve BP control | BP control measured in Clinic BP as measured at baseline, 2 month, 4 month and 6 month and ABP measured at baseline and 6 month | To determine which of the three single pill combinations of two antihypertensive agents is most effective in increasing the proportion of patients who achieve BP control defined as BP: \<140/90 mmHg and \<130/80mmHg at any of their clinic visits and maintained at the 6-month clinic visit. |
| Proportion of patients classified as responders | Clinic BP as measured at baseline, 2 month, 4 month and 6 month | Proportion of patients classified as responders defined as those who had a reduction of SBP ≥20mmHg and DBP ≥10 mmHg at any of their clinic visits and maintained at the 6-month clinic visit. |
| Micro- and macro-albuminuria | Change in serum albumin measured at baseline and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on Micro- and macro-albuminuria. |
| Fasting blood glucose | Change in fasting blood glucose measured at baseline and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on Fasting blood glucose. |
| 24-hour ambulatory diastolic blood pressure | Change in between baseline and 6 month Ambulatory Diastolic Blood Pressure | To determine which of three single pill combinations of two antihypertensive agents is most effective in reducing 24-hour ambulatory diastolic blood pressure at 6 months adjusted for baseline ADBP |
| Serum sodium | Change in serum sodium measured at baseline and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on serum sodium |
| Serum potassium | Change in serum potassium measured at baseline and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on serum potassium |
| Serum urea | Change in serum urea measured at baseline and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on serum urea |
| Serum creatinine | Change in serum creatinine measured at baseline and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on serum creatinine |
| eGFR | Change in eGFR measured at baseline and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on eGFR |
| Adverse events causing trial withdrawal | adverse events causing withdrawal at 2 month, 4 month and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on adverse events causing trial withdrawal |
| renin and aldosterone | Change in plasme renin and/or aldosterone measured at baseline and 6 month | To determine whether baseline plasma renin and/or aldosterone predicts any differential BP effects of the three single-pill combinations under investigation. |
| Fasting lipid profile | Change in serum lipid profile measured at baseline and 6 month | To determine the effect of three single pill combinations of two antihypertensive agents on fasting lipid profile. |
Countries
India
Outcome results
None listed