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
Protocol number: 2016CV12
EValuatIng DiurEtics in Normal CarE (EVIDENCE) - a cluster randomised evaluation of hypertension prescribing policy
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.
East of Scotland Research Ethics Service (EoSRES), 04/01/2017, ref: 17/ES/0016
Two-arm cluster randomised study of prescribing policy
Primary study design
Secondary study design
Cluster randomised trial
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.
Primary outcome measures
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
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
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
Trial participating centre
Medicines Monitoring Unit
University of Dundee Ninewells Hospital and Medical School
University of Dundee/NHS Tayside
TASC (Tayside Medical Science Centre)
Ninewells Hospital & Medical School
TASC Research & Development Office
George Pirie Way
+44 1382 383140
Medicines Monitoring Unit University of Dundee
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
Results - basic reporting