Condition category
Circulatory System
Date applied
29/07/2013
Date assigned
16/08/2013
Last edited
12/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Allopurinol is a medication used to prevent gout. Allopurinol has several positive effects on heart and blood vessels, is inexpensive and is already widely used in patients. Ischaemic heart disease (heart attack) is the most common cause of death in people in the UK and treatment of patients with ischaemic heart disease costs the NHS billions of pounds each year. In this study, we want to improve the treatment of patients with ischaemic heart disease. We want to investigate whether adding allopurinol to these patients’ usual medications will reduce their risk of having a stroke, heart attack or of dying due to cardiovascular disease.

Who can participate?
Patients 60 years and over with ischaemic heart disease (IHD) can participate in the study

What does the study involve?
Patients will attend their local primary care centre (general practice) to take part in the study. Patients will be randomly allocated to receive 600mg daily allopurinol (300mg daily in those patients with mild to moderate renal impairment at screening) or no treatment in addition to their usual medications. They will then will be followed up for a period of around 4 years to count the number of heart attacks, strokes and cardiovascular deaths that occur. The numbers of these events that occur in different treatment groups will be compared to see if there is a benefit of adding allopurinol to their ongoing treatment. Most of the follow-up information will be collected electronically by accessing centrally held electronic records of hospital admissions and deaths, which will make the study easier for patients and more cost-efficient. We will also measure the quality of life and whether there is a cost benefit of using allopurinol in patients with ischaemic heart disease.

What are the possible benefits and risks of participating?
Although we are doing the study to find out whether allopurinol reduces the risk of heart attack, stroke and cardiovascular death in patients with ischaemic heart disease, there may be no direct benefit to a patient of taking part in this study. Some patients might experience side effects due to taking allopurinol, for example, rash, nausea or vomiting.

Where is the study run from?
Medicines Monitoring Unit (MEMO), University of Dundee/Ninewells Hospital (lead centre) and eight other hospitals in Northern England and Scotland (UK)

When is study starting and how long is it expected to run for?
September 2013 to May 2019

Who is funding the study?
National Institute of Health Research (UK)

Who is the main contact?
Dr Isla Mackenzie
isla@memo.dundee.ac.uk

Trial website

http://allheartstudy.org

Contact information

Type

Scientific

Primary contact

Dr Isla Mackenzie

ORCID ID

http://orcid.org/0000-0002-3680-7127

Contact details

MEMO/HRC
University of Dundee
Level 7
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Additional identifiers

EudraCT number

2013-003559-39

ClinicalTrials.gov number

Protocol/serial number

HTA 11/36/41

Study information

Scientific title

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease (ALL-HEART): a randomised controlled trial

Acronym

ALL-HEART

Study hypothesis

The hypothesis of the study is that adding allopurinol 600mg daily to usual therapy will improve cardiovascular outcomes in patients aged over 60 with ischaemic heart disease.

Ethics approval

East of Scotland Research Ethics Service, 16/09/2013, ref: 13/ES/0104

Study design

Multi-centre controlled prospective randomised open-label blinded endpoint (PROBE) trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Prevention

Patient information sheet

Participant information sheet will be available on http://allheartstudy.org or can be requested using the contact details below (once all regulatory approvals have been obtained).

Condition

Ischaemic heart disease (IHD)

Intervention

Interventions as of 04/04/2016:
Patients are randomised to two groups:
1. Receive standard care plus allopurinol (600 mg daily) (Allopurinol dose will be lower at 300mg daily in those patients with mild to moderate renal impairment at screening)
2. Standard care alone
They will be followed up for a period of around 4 years. Most of the follow up data will be
collected electronically by accessing centrally held electronic records of hospital admissions and
deaths

Original interventions:
Patients are randomised to two groups:
1. Receive standard care plus allopurinol (600 mg daily)
2. Standard care alone
They will be followed up for a period of around 4 years. Most of the follow up data will be collected electronically by accessing centrally held electronic records of hospital admissions and deaths

Intervention type

Drug

Phase

Not Applicable

Drug names

Allopurinol

Primary outcome measures

Composite (APTC) CV endpoint of non-fatal myocardial infarction (MI), non-fatal stroke and CV death is determined by record-linkage supported by information from medical records

Secondary outcome measures

1. Non-fatal MI
2. Non-fatal stroke
3. CV death
4. All-cause mortality
5. All CV hospitalisations
6. Hospitalisation for acute coronary syndrome (ACS)
7. Coronary revascularisation
8. Hospitalisation for ACS or revascularisation
9. Hospitalisation for heart failure
10. Quality of life and cost effectiveness of allopurinol

The secondary outcome measures 1-9 will primarily be determined by record-linkage supported by information from medical records. Quality of life is assessed by EQ-5D and Seattle Angina Questionnaires at 0, 1 and 5 years. The cost-effectiveness analysis is supported by information from service usage questionnaires at 1 and 5 years and additionally at 2, 3 and 4 years in a 25% sample of the study population.

Overall trial start date

01/09/2013

Overall trial end date

31/05/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male or female patients aged 60 years and over
2. Ischaemic heart disease (IHD) defined as a diagnosis of angina or myocardial infarction (MI) at any time or other evidence ofischaemic heart disease (investigator opinion)

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

5215

Participant exclusion criteria

1. History of gout
2. Known severe renal impairment (eGFR <30ml/min)
3. Moderate to severe heart failure (NYHA III-IV)
4. Significant hepatic disease (eg ALT >3 x upper limit of normal, cirrhosis, ascites) (investigator opinion)
5. Patients currently taking part in another interventional clinical trial of an investigational medicinal product or medical device (or taken part in one within the last 3 months)
6. Previous allergy to allopurinol
7. Previous serious adverse cutaneous (skin) reaction to any drug (eg Stevens Johnson syndrome, toxic epidermal necrolysis, hospitalisation due to skin reaction to drug) (investigator opinion)
8. Patients already taking urate lowering therapy (including allopurinol, febuxostat, sulfinpyrazone, benzbromarone, probenecid, rasburicase)
9. Patients taking azathioprine, mercaptopurine, ciclosporin or theophylline
10. Malignancy (except non-metastatic, non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years (investigator opinion)

Recruitment start date

01/09/2013

Recruitment end date

31/05/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Medicines Monitoring Unit (MEMO)
University of Dundee Level 7 Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Trial participating centre

Nottingham Digestive Diseases Centre
University Hospital Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Aberdeen Royal Infirmary
Clinical Pharmacology Unit Orange Zone Level 4 Foresterhill
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

University Hospital Crosshouse
Department of Research & Development NHS Ayrshire & Arran 58 Lister Street
Kilmarnock
KA2 OBE
United Kingdom

Trial participating centre

Dumfries & Galloway Royal Infirmary
Research & Development Support Unit Ground Floor Bankend Road
Dumfries
DG1 4AP
United Kingdom

Trial participating centre

Royal Infirmary Edinburgh
Clinical Research Facility Little France
Edinburgh
EH16 4SA
United Kingdom

Trial participating centre

West Glasgow Ambulatory Care Hospital
Clinical Research & Development Dalnair Street
Glasgow
G3 8SW
United Kingdom

Trial participating centre

Raigmore Hospital
Research & Development Deparment Centre for Health Science
Inverness
IV2 3JH
United Kingdom

Trial participating centre

NIHR Clinical Research Network: North East and North Cumbria
Regent Farm Road Gosforth
Newcastle upon Tyne
NE3 3HD
United Kingdom

Sponsor information

Organisation

The University of Dundee (UK)

Sponsor details

c/o Catrina Forde
Tayside medical Sciences Centre (TASC)
Level 4 Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The trial results will be reported in a peer-reviewed journal and at major scientific and clinical meetings. A non-technical summary of the results will also be produced to be sent to patients who participated in the trial, patient groups and cardiovascular charities, as well as communication of the results to the wider public via the media. Copies of the results will be sent to guideline groups for consideration and incorporation into revisions of guidelines.

Intention to publish date

31/12/2021

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27609859

Publication citations

Additional files

Editorial Notes

12/09/2016: Publication reference added. 03/05/2016: Further trial participating centres in Nottingham, Aberdeen, Ayrshire & Arran, Dumfries and Galloway, Edinburgh, Glasgow, Inverness and Newcastle have been added. Ethics approval information added. 20/04/2016: On 04/04/2016, a protocol amendment was implemented to allow the inclusion of patients with mild to moderate renal impairment in the study. Exclusion criterion 2 has been amended from ‘Known renal impairment (eGFR<60ml/min)’ to ‘Known severe renal impairment (eGFR <30ml/min)’. Patients with eGFR 30-59ml/min at their screening visit will receive a maximum dose of 300mg daily allopurinol in the study (instead of 600mg daily) - the interventions section has been updated to reflect this.