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

Primary Hypertension Clinical Trial

— TOPSPIN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05683301
• Other study ID #: CCDC-2022-001
• Status: Recruiting
• Phase: Phase 4
• Start date: August 30, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2023
• Source: Centre for Chronic Disease Control, India
• Contact: Kavita Singh, PhD
• Phone: 011-41618456
• Email: kavita[@]ccdcindia.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 15 hospitals in India. Single Pill combinations (SPCs): 1) Amlodipine + Perindopril, 2) Perindopril + Indapamide, 3) Amlodipine + Indapamide

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 information / eligibility

• Status: Recruiting
• Enrollment: 1968
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 79 Years

Eligibility

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. -

Related Conditions & MeSH terms

• Essential Hypertension
• Primary Hypertension

Intervention

Drug:
• Amlodipine + Perindopril
Single pill combination of dual antihypertensive agent
• Perindopril + Indapamide
Single pill combination of dual antihypertensive agent
• Amlodipine + Indapamide
Single pill combination of dual antihypertensive agent

Locations

Country	Name	City	State
India	Rudraksha Hospital	Ahmedabad	Gujrat
India	Madras Medical College	Chennai	Tamil Nadu
India	Sri Ramchandra Institute of Higher Education and Research	Chennai	Tamil Nadu
India	SDM College of Medical Sciences & Hospital	Dharwad	Karnataka
India	Lisie Hospital	Ernakulam	Kerela
India	Lalitha Super Specialities Hospital	Guntur	Andhra Pradesh
India	Apollo-Excelcare Hospital	Guwahati	Assam
India	All India Institute of Medical Sciences	Jodhpur	Rajasthan
India	Dayanand Medical College and Hospital	Ludhiana	Punjab
India	JSS Hospital	Mysore	Karnataka
India	Sengupta Hospital & Research Institute	Nagpur	Maharashtra
India	All India Institute of Medical Sciences	New Delhi	Delhi
India	Lakshmi Hospital	Palakkad	Kerela
India	North Eastern Indira Gandhi Regional Institute of Medical Sciences	Shillong	Meghalaya

Sponsors (3)

Lead Sponsor	Collaborator
Centre for Chronic Disease Control, India	All India Institute of Medical Sciences, New Delhi, Imperial College London

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Change in between baseline and 6 month Ambulatory Diastolic Blood Pressure
Secondary	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	Comparison of Clinic blood pressure measured at baseline 2 month , 4 month and 6 month
Secondary	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	Change in between baseline and 6 month ASBP and ADBP
Secondary	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	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
Secondary	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.	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
Secondary	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.	Clinic BP as measured at baseline, 2 month, 4 month and 6 month
Secondary	Micro- and macro-albuminuria	To determine the effect of three single pill combinations of two antihypertensive agents on Micro- and macro-albuminuria.	Change in serum albumin measured at baseline and 6 month
Secondary	Fasting blood glucose	To determine the effect of three single pill combinations of two antihypertensive agents on Fasting blood glucose.	Change in fasting blood glucose measured at baseline and 6 month
Secondary	Fasting lipid profile	To determine the effect of three single pill combinations of two antihypertensive agents on fasting lipid profile.	Change in serum lipid profile measured at baseline and 6 month
Secondary	Serum sodium	To determine the effect of three single pill combinations of two antihypertensive agents on serum sodium	Change in serum sodium measured at baseline and 6 month
Secondary	Serum potassium	To determine the effect of three single pill combinations of two antihypertensive agents on serum potassium	Change in serum potassium measured at baseline and 6 month
Secondary	Serum urea	To determine the effect of three single pill combinations of two antihypertensive agents on serum urea	Change in serum urea measured at baseline and 6 month
Secondary	Serum creatinine	To determine the effect of three single pill combinations of two antihypertensive agents on serum creatinine	Change in serum creatinine measured at baseline and 6 month
Secondary	eGFR	To determine the effect of three single pill combinations of two antihypertensive agents on eGFR	Change in eGFR measured at baseline and 6 month
Secondary	Adverse events causing trial withdrawal	To determine the effect of three single pill combinations of two antihypertensive agents on adverse events causing trial withdrawal	adverse events causing withdrawal at 2 month, 4 month and 6 month
Secondary	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.	Change in plasme renin and/or aldosterone measured at baseline and 6 month