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

NCT05683301 | Completed Phase 4 DMC

• 1 other identifier: CCDC-2022-001
• Study Type: interventional
• Target: 1,981
• Locations: 1 country
• Sites: 35

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

Conditions

Primary Hypertension

Outcome Measures

Primary Outcomes (1)

• 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.

  Change in between baseline and 6 month Ambulatory Systolic Blood Pressure

Secondary Outcomes (16)

• 24-hour ambulatory diastolic blood pressure

  Change in between baseline and 6 month Ambulatory Diastolic Blood Pressure

• Clinic Blood Pressure

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

• Daytime and nighttime Blood Pressure

  Change in between baseline and 6 month ASBP and ADBP

• 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

• 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

Study Arms (3)

Arm 1

EXPERIMENTAL

(Arm 1 compare to Arm 2 compare to Arm 3) - Treatment Period 1 (Enrollment - 2 months) - Single Pill Combination of Amlodipine 5 mg and Perindopril 4 mg once daily, orally Treatment Period 2 (2 months - 6 months) - Single Pill Combination of Amlodipine 10 mg and Perindopril 8 mg once daily, orally

Drug: Amlodipine + Perindopril

Arm 2

EXPERIMENTAL

(Arm 1 compare to Arm 2 compare to Arm 3) - Treatment Period 1 (Enrollment - 2 months) - Single Pill Combination of Perindopril 4 mg and Indapamide 1.25 mg once daily, orally Treatment Period 2 (2 months - 6 months) - Single Pill Combination of Perindopril 8 mg and Indapamide 2.5 mg once daily, orally

Drug: Perindopril + Indapamide

Arm 3

EXPERIMENTAL

(Arm 1 compare to Arm 2 compare to Arm 3) - Treatment Period 1 (Enrollment - 2 months) - Single Pill Combination of Amlodipine 5 mg and Indapamide 1.5 mg sustained release once daily, orally Treatment Period 2 (2 months - 6 months) - Single Pill Combination of Amlodipine 10 mg and Indapamide 1.5 mg sustained release once daily, orally

Drug: Amlodipine + Indapamide

Interventions

Amlodipine + Perindopril DRUG

Single pill combination of dual antihypertensive agent

Arm 1

Perindopril + Indapamide DRUG

Single pill combination of dual antihypertensive agent

Arm 2

Amlodipine + Indapamide DRUG

Single pill combination of dual antihypertensive agent

Arm 3

Eligibility Criteria

• Age: 30 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 30-79 years AND
• Sitting clinic values\* of SBP ≥140 mmHg and \<160 mmHg on one antihypertensive agent OR
• Sitting clinic values\* of SBP ≥150 mmHg and \<180 mmHg on no antihypertensive treatment \* Mean of the last 2 of 3 readings.

You may not qualify if:

• Congestive heart failure (clinically defined).
• Patients with a history of intolerance to any of the study medications for example angioedema or dry cough with Angiotensin-converting enzyme inhibitors.
• Serum creatinine levels greater than 132.6µmol/l (1.5mg/dl)
• \. History of coronary heart disease (i.e., chronic stable angina, myocardial infarction or acute coronary syndrome).
• History of a stroke or other cerebrovascular accident (i.e. transient ischaemic attack or reversible ischaemic neurological deficit).
• Severe hepatic impairment
• Treatment with agents causing torsades de pointes
• Lactation
• Contraindications to any of the investigational medicinal products as per the summaries product characteristics of drugs studied
• Known or suspected secondary hypertension.
• Any other concomitant illness, physical or mental impairment that could interfere with the effective conduct of the study.
• Pregnancy or those of child-bearing age who are not taking reliable contraception.
• History of Gout.
• Serum potassium \< 3.5mmol/L at screening.

Sponsors & Collaborators

• Centre for Chronic Disease Control, India: lead
• All India Institute of Medical Sciences: collaborator
• Imperial College London: collaborator

Study Sites (35)

Lalitha Super Specialities Hospital

Guntur, Andhra Pradesh, 522001, India

Location

Apollo Hospitals

Visakhapatnam, Andhra Pradesh, 530002, India

Location

Assam Medical College

Dibrugarh, Assam, 786002, India

Location

Apollo-Excelcare Hospital

Guwahati, Assam, 781033, India

Location

Rudraksha Hospital

Ahmedabad, Gujarat, 382425, India

Location

Apollo Hospitals

Ahmedabad, Gujarat, 382428, India

Location

Aman Hospital & Research Center

Vadodara, Gujarat, 390021, India

Location

Lifecare Hospital & Research Centre

Bangalore, Karnataka, 560092, India

Location

SDM College of Medical Sciences & Hospital

Dharwad, Karnataka, 580009, India

Location

Indiana Hospital & Heart Institute

Mangalore, Karnataka, 575002, India

Location

JSS Hospital

Mysore, Karnataka, 570004, India

Location

BLDE, Shri B. M. Patil Medical College, Hospital & Research Centre

Vijayapura, Karnataka, 586103, India

Location

Lisie Hospital

Ernākulam, Kerala, 682018, India

Location

Lakshmi Hospital

Palakkad, Kerala, 678013, India

Location

BKL Walawalkar Rural Medical College and Hospital

Devran, Maharashtra, 415606, India

Location

Bhatia Hospital

Mumbai, Maharashtra, 400007, India

Location

Sengupta Hospital & Research Institute

Nagpur, Maharashtra, 440033, India

Location

Shalinitai Meghe Hospital and Research Center

Nagpur, Maharashtra, 441110, India

Location

Nazareth Hospital

Shillong, Meghālaya, 793003, India

Location

North Eastern Indira Gandhi Regional Institute of Medical Sciences

Shillong, Meghālaya, 793018, India

Location

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Indraprastha Apollo Hospitals

New Delhi, National Capital Territory of Delhi, 110076, India

Location

Apollo Hospitals

Bhubaneshwar, Odisha, 751005, India

Location

All India Institute of Medical Sciences

Bathinda, Punjab, 151001, India

Location

Dayanand Medical College and Hospital

Ludhiana, Punjab, 141001, India

Location

Sadbhavna Medical and Heart Institute

Patiāla, Punjab, 147001, India

Location

SP Medical College

Bikaner, Rajasthan, 334001, India

Location

All India Institute of Medical Sciences

Jodhpur, Rajasthan, 342005, India

Location

Madras Medical College

Chennai, Tamil Nadu, 600003, India

Location

Sri Ramchandra Institute of Higher Education and Research

Chennai, Tamil Nadu, 600116, India

Location

Apollo Hospital

Madurai, Tamil Nadu, 625020, India

Location

Osmania General Hospital

Hyderabad, Telangana, 500007, India

Location

Apollo DRDO Hospitals

Hyderabad, Telangana, 500058, India

Location

Apollo Institute of Medical Sciences

Hyderabad, Telangana, 500090, India

Location

Mediciti Institute of Medical Sciences

Hyderabad, Telangana, 501401, India

Location

Related Publications (1)

• Prabhakaran D, Roy A, Chandrasekaran AM, Kondal D, Mukherjee S, Kiru G, Singh K, Salwa H, Sobitharaj EC, Lobo AS, Mahajan G, Mohan B, Khanna A, Malviya A, Patil SG, Abichandani VK, Singh B, Gupta BK, Yellapantula B, Dandge S, Sengupta S, Kumar S, Bardoloi N, Senguttuvan NB, Sahay RK, Patil S, Deora S, Prahalad R, Sarvepalli VP, Gnanaraj JP, Khanna M, Mishra A, Aithal K, Chavda V, Cornelius VR; TOPSPIN Clinical Consortia; Poulter NR. Comparison of dual therapies for hypertension treatment in India: a randomized clinical trial. Nat Med. 2025 Sep;31(9):3169-3175. doi: 10.1038/s41591-025-03854-w. Epub 2025 Jul 25.

  PMID: 40715816 DERIVED

MeSH Terms

Conditions

Essential Hypertension

Interventions

amlodipine, perindopril drug combination; indapamide, perindopril drug combination; Amlodipine; Indapamide

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Dorairaj Prabhakaran, DM Cardiology

  Centre for Chronic Disease Control, New Delhi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Director

Study Record Dates

• First Submitted: December 10, 2022
• First Posted: January 13, 2023
• Study Start: August 30, 2022
• Primary Completion: August 30, 2024
• Study Completion: September 22, 2024
• Last Updated: October 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: 01-09-2025 till 30-09-2030
• Access Criteria: Only bonafide researchers with a valid research question shall be provided data. Interested researchers shall write to Prof. Prabhakaran (dprabhakaran@ccdcindia.org) with a concept note and necessary approvals as applicable.

Locations

IN (35)