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

Registration Number
NCT05683301
Lead Sponsor
Centre for Chronic Disease Control, India
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1981
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)

    1. History of coronary heart disease (i.e., chronic stable angina, myocardial infarction or acute coronary syndrome).
  4. History of a stroke or other cerebrovascular accident (i.e. transient ischaemic attack or reversible ischaemic neurological deficit).

  5. Severe hepatic impairment

  6. Treatment with agents causing torsades de pointes

  7. Lactation

  8. Contraindications to any of the investigational medicinal products as per the summaries product characteristics of drugs studied

  9. Known or suspected secondary hypertension.

  10. Any other concomitant illness, physical or mental impairment that could interfere with the effective conduct of the study.

  11. Pregnancy or those of child-bearing age who are not taking reliable contraception.

  12. History of Gout.

  13. Serum potassium < 3.5mmol/L at screening.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2Perindopril + Indapamide(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
Arm 3Amlodipine + Indapamide(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
Arm 1Amlodipine + Perindopril(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
Primary Outcome Measures
NameTimeMethod
24-hour ambulatory systolic Blood PressureChange 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 Outcome Measures
NameTimeMethod
Serum creatinineChange 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

eGFRChange in eGFR measured at baseline and 6 month

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

renin and aldosteroneChange 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.

Serum potassiumChange 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

24-hour ambulatory diastolic blood pressureChange 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

Clinic Blood PressureComparison 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 PressureChange 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 BPsFluctuations 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

Micro- and macro-albuminuriaChange 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.

Proportion of patients who achieve BP controlBP 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.

Fasting blood glucoseChange 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.

Serum sodiumChange 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 ureaChange 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

Adverse events causing trial withdrawaladverse 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

Fasting lipid profileChange 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.

Trial Locations

Locations (31)

Apollo Hospitals

🇮🇳

Bhubaneshwar, Odisha, India

Assam Medical College

🇮🇳

Dibrugarh, Assam, India

Indraprastha Apollo Hospitals

🇮🇳

New Delhi, Delhi, India

Aman Hospital & Research Center

🇮🇳

Vadodara, Gujarat, India

Lifecare Hospital & Research Centre

🇮🇳

Bangalore, Karnataka, India

Indiana Hospital & Heart Institute

🇮🇳

Mangalore, Karnataka, India

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

🇮🇳

Vijayapura, Karnataka, India

BKL Walawalkar Rural Medical College and Hospital

🇮🇳

Devran, Maharashtra, India

Bhatia Hospital

🇮🇳

Mumbai, Maharashtra, India

Shalinitai Meghe Hospital and Research Center

🇮🇳

Nagpur, Maharashtra, India

Nazareth Hospital

🇮🇳

Shillong, Meghalaya, India

Sadbhavna Medical and Heart Institute

🇮🇳

Patiala, Punjab, India

SP Medical College

🇮🇳

Bikaner, Rajasthan, India

Apollo Hospital

🇮🇳

Madurai, Tamil Nadu, India

Osmania General Hospital

🇮🇳

Hyderabad, Telangana, India

Apollo DRDO Hospitals

🇮🇳

Hyderabad, Telangana, India

Apollo Institute of Medical Sciences

🇮🇳

Hyderabad, Telangana, India

Mediciti Institute of Medical Sciences

🇮🇳

Hyderabad, Telangana, India

Lalitha Super Specialities Hospital

🇮🇳

Guntur, Andhra Pradesh, India

Apollo-Excelcare Hospital

🇮🇳

Guwahati, Assam, India

All India Institute of Medical Sciences

🇮🇳

Jodhpur, Rajasthan, India

Rudraksha Hospital

🇮🇳

Ahmedabad, Gujrat, India

SDM College of Medical Sciences & Hospital

🇮🇳

Dharwad, Karnataka, India

JSS Hospital

🇮🇳

Mysore, Karnataka, India

Lisie Hospital

🇮🇳

Ernakulam, Kerela, India

Lakshmi Hospital

🇮🇳

Palakkad, Kerela, India

Sengupta Hospital & Research Institute

🇮🇳

Nagpur, Maharashtra, India

North Eastern Indira Gandhi Regional Institute of Medical Sciences

🇮🇳

Shillong, Meghalaya, India

Dayanand Medical College and Hospital

🇮🇳

Ludhiāna, Punjab, India

Madras Medical College

🇮🇳

Chennai, Tamil Nadu, India

Sri Ramchandra Institute of Higher Education and Research

🇮🇳

Chennai, Tamil Nadu, India

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