Primary Care Strategies to Reduce High Blood Pressure: A Cluster Randomized Trial in Rural Bangladesh, Pakistan and Sri Lanka (COBRA-BPS)

Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan and Sri Lanka (COBRA-BPS)

Background: High blood pressure (BP) is the leading attributable risk for cardiovascular disease (CVD). In rural South Asia, hypertension remains to be a significant public health issue with sub-optimal rates of case finding and management. The goal of the full-scale study is to evaluate the effectiveness and cost-effectiveness of multicomponent primary care strategies on lowering blood pressure among adults with hypertension in rural communities in Bangladesh, Pakistan, and Sri Lanka.

Methods/Design: The mixed-methods, stratified cluster randomized controlled trial

Intervention: The multi-component interventions (MCI) is comprised of all the following five components: 1) home health education (HHE) by government community health workers (CHWs), plus 2) blood pressure (BP) monitoring and stepped-up referral to a trained general practitioner (GP) using a checklist, plus 3) training public and private providers in management of hypertension and using a checklist, plus 4) designating hypertension triage counter and hypertension care coordinators in government clinics, plus 5) a financing model to compensate for additional health services and provide subsides to low income individuals with poorly controlled hypertension.

Usual care: Will comprise existing services in the community without any additional training.

Participants: The trial will be conducted on 2550 individuals aged 40 years or older with hypertension (systolic BP ≥ 140 mm Hg or diastolic BP≥ 90 mm Hg, or on antihypertensive therapy) in 30 rural communities of Bangladesh, Pakistan and Sri Lanka. Out of the 2550 individuals, 420 with poorly controlled BP (Systolic BP≥160 mmHg or Diastolic BP≥100 mmHg) will be selected, 14 from each community, to investigate the effect of MCI on results from ambulatory BP monitoring.

Qualitative component: Stakeholders including policymakers, district managers, and community health workers, GPs, hypertensive individuals and family members in the identified clusters will be surveyed.

Outcome: The primary outcome will be change in systolic BP from baseline to follow-up at 24 months post randomization. The cost effectiveness outcome is the incremental cost of MCI per unit reduction in BP over the two year time period and in terms of incremental cost per CVD DALYs averted.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Other: multi-component interventions

• Study Type: Interventional
• Enrollment (Anticipated): 2550
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main study:

Inclusion Criteria:

1. Age≥ 40 years
2. Residing in the selected clusters

3. Hypertension defined either as:

   1. Persistently elevated BP (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg) from each set of last 2 of 3 readings from 2 separate days
   2. maintained on anti-hypertensive medications
4. Informed consent

Exclusion Criteria:

1. Permanently bed-ridden individuals too ill to commute to the clinic
2. Pregnancy, or individuals with advanced medical disease (on dialysis, liver failure, other systemic diseases)
3. Individuals that are mentally compromised and unable to give informed consent

Sub-study:

1) fulfill all criteria of main study and, 2) Persistently elevated systolic BP >160 mm Hg or diastolic BP >100 mm Hg from each set of 2 readings from 2 separate days

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: usual care; Usual care comprises existing services for hypertension control in the community without any additional training
Experimental: multi-component interventions; : The multi-component interventions (MCI) is comprised of all the following five components: 1) home health education (HHE) by government community health workers (CHWs), plus 2) blood pressure (BP) monitoring and stepped-up referral to a trained general practitioner (GP) using a checklist, plus 3) training public and private providers in management of hypertension and using a checklist, plus 4) designating hypertension triage counter and hypertension care coordinators in government clinics, plus 5) a financing model to compensate for additional health services and provide subsides to low income individuals with poorly controlled hypertension.	Other: multi-component interventions; The multi-component interventions (MCI) is comprised of all the following five components: 1) home health education (HHE) by government community health workers (CHWs), plus 2) blood pressure (BP) monitoring and stepped-up referral to a trained general practitioner (GP) using a checklist, plus 3) training public and private providers in management of hypertension and using a checklist, plus 4) designating hypertension triage counter and hypertension care coordinators in government clinics, plus 5) a financing model to compensate for additional health services and provide subsides to low income individuals with poorly controlled hypertension.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood pressure reading:change in systolic blood pressure (SBP) from baseline to follow-up at 24 months post randomization.	Blood pressure (BP) will measured at baseline and then at 6-month intervals until 24 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure reading:Blood Pressure(BP) controlled to target (Systolic BP <140 mm Hg and Diastolic BP <90 mm		at 6-month intervals over 24 months
Questionnaire:Composite outcome of death (all cause), or hospital admission due to coronary heart disease (CHD), heart failure, or stroke		24 months
Questionnaire and EQ-5D-5L:Incremental cost per quality-adjusted life-year (QALY) gained from baseline to end of follow-up		24 months
Morisky Medication Adherence Scale(MMAS):Change in antihypertensive medication adherence (Morisky score)		24 months
Height and weight measurements:change in body mass index ( BMI)		24 months
questionnaire:change dietary salt intake (urinary excretion)		24 months
Questionnaire:change in prevalence of current smokers		24 months
Questionnaire:incident diabetes		24 months
Lipid panel: change in serum lipid levels		24 months
questionnaire: change in INTERHEART cardiovascular disease (CVD) risk score		24 months
Questionnaire:incidence of adverse outcomes (medication side effects, sick days absenteeism, low QALY between randomized groups).		24 months
Questionnaire and serum creatinine:Change in estimated glomerular filtration rate (eGFR)		24 months
Urine albumin:Change in urine albumin		24 months
24 hours mean diastolic BP	Secondary outcome for the sub-study of 420 patients with poorly controlled BP at baseline	24 months
Daytime SBP/DBP	secondary outcome for the sub-study of 420 patients with poorly controlled BP at baseline	24 months
Night time SBP/DBP	Secondary outcome for the sub-study of 420 patients with poorly controlled BP at baseline	24 months
Dipping Pattern	Secondary outcome for the sub-study of 420 patients with poorly controlled BP at baseline	24 months
24 hour BP variability	Secondary outcome for the sub-study of 420 patients with poorly controlled BP at baseline	24 months
Questionnaire and EQ-5D-5L:Incremental cost per mm Hg BP reduction from baseline to end of follow-up at two years post randomization and incremental cost per projected cardiovascular disease ( CVD) disability adjusted life year (DALY) averted		information on healthcare cost will be collected at baseline and 24 months
incremental cost per mm Hg BP reduction from baseline to end of follow-up at 2 years post-randomization and incremental cost per projected CVD disability-adjusted life year (DALY) averted		24 months

Collaborators and Investigators

• Sponsor: Duke-NUS Graduate Medical School
• Collaborators: Aga Khan University; International Centre for Diarrhoeal Disease Research, Bangladesh; University of Kelaniya
• Investigators: Principal Investigator: Tazeen H Jafar, MD,MPH, Duke-NUS Medical School (Singapore)

Publications and helpful links

General Publications

• Feng L, Jehan I, de Silva HA, Naheed A, Khan AH, Kasturiratne A, Clemens JD, Lim CW, Hughes AD, Chaturvedi N, Jafar TH. Effect of a Multicomponent Intervention on Antihypertensive Medication Intensification in Rural South Asia: Post Hoc Analysis of a Cluster RCT. Am J Hypertens. 2021 Sep 22;34(9):981-988. doi: 10.1093/ajh/hpab072.
• Jafar TH, Gandhi M, de Silva HA, Jehan I, Naheed A, Finkelstein EA, Turner EL, Morisky D, Kasturiratne A, Khan AH, Clemens JD, Ebrahim S, Assam PN, Feng L; COBRA-BPS Study Group. A Community-Based Intervention for Managing Hypertension in Rural South Asia. N Engl J Med. 2020 Feb 20;382(8):717-726. doi: 10.1056/NEJMoa1911965.
• Perera M, de Silva CK, Tavajoh S, Kasturiratne A, Luke NV, Ediriweera DS, Ranasinha CD, Legido-Quigley H, de Silva HA, Jafar TH. Patient perspectives on hypertension management in health system of Sri Lanka: a qualitative study. BMJ Open. 2019 Oct 7;9(10):e031773. doi: 10.1136/bmjopen-2019-031773.
• Gandhi M, Assam PN, Turner EL, Morisky DE, Chan E, Jafar TH; COBRA-BPS Study Group. Statistical analysis plan for the control of blood pressure and risk attenuation-rural Bangladesh, Pakistan, Sri Lanka (COBRA-BPS) trial: a cluster randomized trial for a multicomponent intervention versus usual care in hypertensive patients. Trials. 2018 Nov 29;19(1):658. doi: 10.1186/s13063-018-3022-8.
• Feng L, de Silva HA, Jehan I, Naheed A, Kasturiratne A, Himani G, Hasnat MA, Jafar TH. Regional variation in chronic kidney disease and associated factors in hypertensive individuals in rural South Asia: findings from control of blood pressure and risk attenuation-Bangladesh, Pakistan and Sri Lanka. Nephrol Dial Transplant. 2019 Oct 1;34(10):1723-1730. doi: 10.1093/ndt/gfy184.
• Jafar TH, Gandhi M, Jehan I, Naheed A, de Silva HA, Shahab H, Alam D, Luke N, Wee Lim C; COBRA-BPS Study Group. Determinants of Uncontrolled Hypertension in Rural Communities in South Asia-Bangladesh, Pakistan, and Sri Lanka. Am J Hypertens. 2018 Oct 15;31(11):1205-1214. doi: 10.1093/ajh/hpy071.
• Jafar TH, Jehan I, de Silva HA, Naheed A, Gandhi M, Assam P, Finkelstein EA, Quigley HL, Bilger M, Khan AH, Clemens JD, Ebrahim S, Turner EL; for COBRA-BPS Study Group; Kasturiratne A. Multicomponent intervention versus usual care for management of hypertension in rural Bangladesh, Pakistan and Sri Lanka: study protocol for a cluster randomized controlled trial. Trials. 2017 Jun 12;18(1):272. doi: 10.1186/s13063-017-2018-0.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): March 1, 2019
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: January 14, 2016
• First Submitted That Met QC Criteria: January 15, 2016
• First Posted (Estimate): January 18, 2016

Study Record Updates

• Last Update Posted (Actual): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: cardiovascular disease; cost-effectiveness; Antihypertensive agents; high blood pressure; Non-pharmacological treatment; blood pressure monitoring; community health care workers
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: MR/N006178/1