Treatment Optimisation for Blood Pressure With Single-Pill Combinations in India

Centre for Chronic Disease Control, India1,981 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

1,981

Conditions

Primary Hypertension

Interventions

Eligibility

Sex: ALLMin age: 30 YearsMax age: 79 Years

Medical Language ↔ Plain English

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. \-

Locations (35)

Lalitha Super Specialities Hospital

Guntur, Andhra Pradesh, India

Apollo Hospitals

Visakhapatnam, Andhra Pradesh, India

Assam Medical College

Dibrugarh, Assam, India

Apollo-Excelcare Hospital

Guwahati, Assam, India

Rudraksha Hospital

Ahmedabad, Gujarat, India

Apollo Hospitals

Outcomes

Primary Outcomes

24-hour 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.

Time frame: Change in between baseline and 6 month Ambulatory Systolic Blood Pressure

Secondary Outcomes

24-hour 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

Time frame: Change in between baseline and 6 month Ambulatory Diastolic Blood Pressure

Clinic Blood Pressure

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

Time frame: Comparison of Clinic blood pressure measured at baseline 2 month , 4 month and 6 month

Daytime and nighttime Blood Pressure

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

Time frame: Change in between baseline and 6 month ASBP and ADBP

BP variability measured by ABPM and within-visit clinic BPs

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

Time frame: 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

Proportion of patients who achieve BP control

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.

Time frame: 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

Proportion of patients classified as "responders"

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.

Time frame: Clinic BP as measured at baseline, 2 month, 4 month and 6 month

Micro- and macro-albuminuria

To determine the effect of three single pill combinations of two antihypertensive agents on Micro- and macro-albuminuria.

Time frame: Change in serum albumin measured at baseline and 6 month

Fasting blood glucose

To determine the effect of three single pill combinations of two antihypertensive agents on Fasting blood glucose.

Time frame: Change in fasting blood glucose measured at baseline and 6 month

Fasting lipid profile

To determine the effect of three single pill combinations of two antihypertensive agents on fasting lipid profile.

Time frame: Change in serum lipid profile measured at baseline and 6 month

Serum sodium

To determine the effect of three single pill combinations of two antihypertensive agents on serum sodium

Time frame: Change in serum sodium measured at baseline and 6 month

Serum potassium

To determine the effect of three single pill combinations of two antihypertensive agents on serum potassium

Time frame: Change in serum potassium measured at baseline and 6 month

Serum urea

To determine the effect of three single pill combinations of two antihypertensive agents on serum urea

Time frame: Change in serum urea measured at baseline and 6 month

Serum creatinine

To determine the effect of three single pill combinations of two antihypertensive agents on serum creatinine

Time frame: Change in serum creatinine measured at baseline and 6 month

eGFR

To determine the effect of three single pill combinations of two antihypertensive agents on eGFR

Time frame: Change in eGFR measured at baseline and 6 month

Adverse events causing trial withdrawal

To determine the effect of three single pill combinations of two antihypertensive agents on adverse events causing trial withdrawal

Time frame: adverse events causing withdrawal at 2 month, 4 month and 6 month

renin and aldosterone

To determine whether baseline plasma renin and/or aldosterone predicts any differential BP effects of the three single-pill combinations under investigation.

Time frame: Change in plasme renin and/or aldosterone measured at baseline and 6 month