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

Centre for Chronic Disease Control, India

Status and phase: Completed; Phase 4

Conditions: Primary Hypertension

Treatments: Drug: Amlodipine + Indapamide; Drug: Perindopril + Indapamide; Drug: Amlodipine + Perindopril

Study type: Interventional

Funder types: Other

Identifiers

NCT05683301

CCDC-2022-001

Details and patient eligibility

About

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

Full 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.

Enrollment: 1,981 patients

Sex: All

Ages: 30 to 79 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,981 participants in 3 patient groups

Arm 1

Experimental group

Description:

(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

Treatment:

Drug: Amlodipine + Perindopril

Arm 2

Experimental group

Description:

(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

Treatment:

Drug: Perindopril + Indapamide

Arm 3

Experimental group

Description:

(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

Treatment:

Drug: Amlodipine + Indapamide