Condition category
Circulatory System
Date applied
11/01/2012
Date assigned
08/02/2012
Last edited
24/04/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

http://www.hta.ac.uk/2144

Trial website

Contact information

Type

Scientific

Primary contact

Prof John Cleland

ORCID ID

Contact details

Department of Cardiology
Daisy Building
Castle Hill Hospital
Castle Road
Cottingham
Hull
HU16 5JQ
United Kingdom
+44 (0)1482 761776
j.g.cleland@hull.ac.uk

Additional identifiers

EudraCT number

2009-011637-27

ClinicalTrials.gov number

Protocol/serial number

HTA 08/53/36

Study information

Scientific title

A randomised, open-label, study comparing the effects of aspirin and clopidogrel on outcomes in patients with chronic heart failure

Acronym

CACHE

Study hypothesis

Compared to clopidogrel, aspirin has an adverse effect on cardiovascular function in patients with heart failure leading to an increase in the symptoms of heart failure, reduced quality of life, an increase in hospitalisation and higher mortality.

Demonstrating whether such differences do or do not exist would be valuable and settle a substantial controversy in care, highlighted in international guidelines for the management of heart failure. The protocol designed to address this in a non-blinded, randomised controlled trial comparing aspirin and clopidogrel, conducted in 3,000 patients with heart failure over a period of approximately 5 years.

Ethics approval

Northern & Yorkshire REC, 15/05/2012, ref: 10/H0903/13

Study design

Phase IV trial open-label interventional non-blinded randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Heart failure

Intervention

Clopidogrel vs aspirin both 75 mg/day per patient taken orally & daily.

This phase IV trial will compare the effects of prescribing aspirin 75 mg/day and clopidogrel 75 mg/day, primarily on all-cause mortality. Half of the patients will be randomised to each intervention. The investigator and the patient will know to which treatment the patient has been assigned. The duration of the study is determined by the event-rate although it could be stopped early for futility or because of a larger than anticipated treatment difference. The planned mean duration of follow-up is 3.8 years and some patients may be followed for more than five years before the required number of events has been attained. However, to allow for uncertainty we seek permission to follow patients for up to ten years.

Intervention type

Drug

Phase

Phase IV

Drug names

Clopidogrel, aspirin

Primary outcome measure

All causes mortality

Secondary outcome measures

1. Cardiovascular death or hospitalisation for heart failure (time to first event)
2. Sudden death or a vascular event (myocardial infarction, stroke, peripheral embolism, requirement for angioplasty or vascular surgery) using a time to first event analysis
3. Total days lost to death or hospitalisation (all causes)
4. Quality-adjusted years alive (QALY) using repeated measurements of EQ5D
5. Cost per QALY

Overall trial start date

11/02/2011

Overall trial end date

31/08/2016

Reason abandoned (if study stopped)

Participant recruitment issue

Eligibility

Participant inclusion criteria

1. Willing and able to provide written confirmation of informed consent
2. A clinical diagnosis of heart failure
3. Currently in sinus rhythm on clinical examination
4. Receiving diuretics for at least 6 weeks prior to inclusion
5. Patients must have a telephone
6. Patients must be willing to provide their personal contact details, those of their next of kin and those of their general practitioner (GP) and hospital to the national coordinating office and be willing to be contacted by telephone by these staff.
7. Patients must be willing to have hospitalisation and other serious events tracked through mechanisms including:
7.1. In England:
7.1.1. The National Health Service (NHS) Central Register (NHSCR)
7.1.2. National Office of Statistics
7.2. In Scotland:
7.2.1. The Registrar General’s Office
7.2.2. NHS Information Statistics Division
8. If non-English speaking, patients must have a friend or relative who can translate or who have other access to translation

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

3000

Total final enrolment

87

Participant exclusion criteria

1. Plasma (central lab) NT-proBNP <400pg/ml (47.3pmol/L) or MR-proANP <200pmol/L
2. Lack of an ECG within the previous 12 months documenting sinus rhythm. Patients who have had an episode of atrial fibrillation in the previous year may be enrolled provided the most recent ECG shows sinus rhythm and the treating doctor has decided not to prescribe anti-coagulants.
3. Severe valve disease in the investigators opinion (an echocardiogram report within the previous 12 months must be available)
4. Serum creatinine >250umol/L (local lab)
5. Intolerant of aspirin or clopidogrel or who have a contraindication to such treatment or who require anti-coagulation
6. Contraindications to aspirin or clopidogrel include:
6.1. Substantial, in the investigators opinion, bleeding from an uncorrected source within the previous year
6.2. Endoscopically proven peptic ulcer within the previous 3 months. Patients must be on treatment if peptic ulcer diagnosed in previous year
6.3. Haemorrhagic stroke within the previous 3 months
6.4. Known coagulation disorder (e.g. haemophilia)
6.5. Full blood count suggesting iron deficiency (patients may be enrolled in the study after the cause of iron deficiency is or has previously been investigated and treatment has been initiated) (local lab)
7. Platelet count <100,000 (local lab)
8. Scheduled procedure that would require discontinuation of study medication for > 2 weeks (patient may be recruited after procedure)
9. History of uncontrolled seizures or high risks of falls
10. Regular use of non-steroidal anti-inflammatory agents > 3 times a week
11. Use of maintenance oral corticosteroids
12. Women of child-bearing potential or who are breast feeding
13. Patients with a history of asthma should not take part unless they have taken aspirin previously without ill-effect
14. Patients with an indication for oral anti-coagulation including:
14.1 Current or recent (within 12 months) atrial fibrillation or flutter (evidence of an ECG documenting sinus rhythm must be provided)
14.2. Prior embolic stroke
14.3. Mechanical prosthetic heart valve
15. Patients requiring dual anti-platelet therapy including:
15.1. Patients within 3 months of an acute coronary syndrome
15.2. Transient ischaemic attack or vascular procedure or within one year of receiving a drug eluting coronary stent
16. Patients likely to die of something other than heart failure or sudden (cardiac) death
17. Inability to walk without the physical assistance of another person (patients with walking aids are permitted)
18. Other patients deemed unlikely to comply with the protocol
19. Women who are at pregnant or who could become pregnant
20. Women of child-bearing age should be taking reliable contraception (tubal ligation or implanted contraceptive)
21. Inability to communicate in English

Recruitment start date

11/02/2011

Recruitment end date

31/08/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Castle Hill Hospital
Hull
HU16 5JQ
United Kingdom

Sponsor information

Organisation

Hull and East Yorkshire Hospitals NHS Trust (UK)

Sponsor details

Research and Development Department
Daisy Building
Castle Hill Hospital
Castle Road
Hull
HU16 5JQ
United Kingdom
+44 (0)1482 461882
priyai.parkinson@hey.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.hey.nhs.uk/

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

Not provided at time of registration

Intention to publish date

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

2014 results in: https://academic.oup.com/eurheartj/article/35/suppl_1/1/541954 [added 18/04/2019]

Publication citations

Additional files

Editorial Notes

24/04/2019: The trial was stopped due to low recruitment. There are no further plans to publish. 18/04/2019: Publication reference and total final enrolment added.