Condition category
Circulatory System
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Plain English Summary

Background and study aims
Having high blood pressure increases the chances that a person will suffer a heart attack or stroke in the future. The aim of treating high blood pressure with medication is to reduce this risk. A number of different types of medication are known to be effective in reducing blood pressure and in reducing the risk of heart attack and stroke. One of these medication types is the diuretics, often referred to as “water-tablets”. There are two diuretics commonly used in the UK for the treatment of high blood pressure but we do not know which is better. We know that they both work but one may be more effective than the other in the long term. The EVIDENCE (Evaluating Diuretics in Normal Care) study aims to find out if one of these medications is better than the other at preventing heart attacks and strokes. In everyday practice, GP's and hospital doctors are guided by agreed policies, based upon the best available evidence, in deciding which medications are likely to be the most effective. This study aims to compare the effectiveness of two different prescribing policies for diuretics in preventing heart attacks and strokes.

Who can participate?
Patients aged 18 and older who are diagnosed with a thiazide, or thiazide-like diuretic to treat hypertension.

What does the study involve?
Participating GPs are randomly assigned to one of these two prescribing policies. The doctors within that practice then use that policy to guide their prescribing decisions. As already happens in the NHS, mechanisms for switching from one medication to another is used to help practices adhere to their prescribing policy. GP's and their patients are free to choose what they think is the most appropriate treatment in each individual case. People who are registered in practices taking part in the study have their blood pressure medication managed by their GP in the usual way. If the practice policy requires a change to a patient’s usual diuretic prescription, participants are sent a letter advising them that this will take effect on their next requested prescription. All such patients will be given the opportunity to decline the switch. Participants are followed up with for the cardiovascular outcomes.

What are the possible benefits and risks of participating?
As the two medications in question are currently thought to be effectively the same in terms of benefits and side effects, there will be no direct risk or benefit to a person whose GP practice is taking part in the study.

Where is the study run from?
Medicines Monitoring Unit, University of Dundee (UK)

When is the study starting and how long is it expected to run for?
October 2017 to October 2020

Who is funding the study?
University of Dundee (UK)

Who is the main contact?
Dr Amy Rogers

Trial website

Contact information



Primary contact

Dr Amy Rogers


Contact details

Medicines Monitoring Unit
University of Dundee
Medical School
United Kingdom
+44 1382 383390

Additional identifiers

EudraCT number number

Protocol/serial number

Protocol number: 2016CV12

Study information

Scientific title

EValuatIng DiurEtics in Normal CarE (EVIDENCE) - a cluster randomised evaluation of hypertension prescribing policy



Study hypothesis

The aim of this study is to formally evaluate the effectiveness of a policy of prescribing bendroflumethiazide versus a policy of prescribing indapamide as first-line choice of thiazide/thiazide-like diuretic in the treatment of hypertension.

Ethics approval

East of Scotland Research Ethics Service (EoSRES), 04/01/2017, ref: 17/ES/0016

Study design

Two-arm cluster randomised study of prescribing policy

Primary study design


Secondary study design

Cluster randomised trial

Trial setting

GP practices

Trial type


Patient information sheet

No participant information sheet available


Hypertension and cardiovascular risk


There are two study arms. Practices are randomly assigned on a 1:1 basis (using a computer algorithm) to either of two prescribing policies:

1. A policy of using Bendroflumethiazide (2.5mg, oral, once daily) as first choice when a diuretic is required for the treatment of hypertension

2. A policy of using Indapamide (2.5mg, immediate release, oral, once daily) as first choice when a diuretic is required for the treatment of hypertension

Individual treatment decisions regarding drug choice, dosage, method and frequency of administration for patients will be left up to the treating GPs.

Where patients are already taking thiazide, or thiazide-like, diuretics at the time a practice joins the study, routine repeat prescriptions will be switched to the policy preferred drug, unless clinically indicated.

Intervention type



Drug names

Primary outcome measure

The composite cardiovascular outcome (comprising non-fatal MI, non-fatal stroke, hospitalization for congestive heart failure, and vascular death) is measured using electronic record-linkage to national datasets of routinely collected data and supported by information from medical records.

Secondary outcome measures

1. Each individual component of the composite primary outcome will be included as a secondary outcome
2. All-cause mortality is measured using record-linkage to national datasets of routinely collected data

The study is primary outcome driven so the outcomes are counted as they occur rather than at defined time periods. We expect that the follow-up process will take around 3 years to accrue sufficient events to power the study.

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Registered patients with a documented diagnosis of hypertension and prescribed a thiazide, or thiazide-like, diuretic in a participating practice
2. Aged 18 and older

Participant type


Age group




Target number of participants

215 GP practices of typical size (including approximately 240 individuals prescribed diuretics for hypertension)

Participant exclusion criteria

Not meeting the inclusion criteria.

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Medicines Monitoring Unit
University of Dundee Ninewells Hospital and Medical School
United Kingdom

Sponsor information


University of Dundee/NHS Tayside

Sponsor details

TASC (Tayside Medical Science Centre)
Ninewells Hospital & Medical School
TASC Research & Development Office
Level 3
George Pirie Way
United Kingdom
+44 1382 383140

Sponsor type




Funder type

Research council

Funder name

Medicines Monitoring Unit University of Dundee

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

We will publish the study protocol (where possible) and will undertake to make public the study results. The major form of publication will be articles in scientific journals but presentations and press releases may also be made. Protocol and statistical analysis plan will be made available at a later date.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date


Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes