| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The objective of this study is to determine whether treating patients who have heart failure with clopidogrel 75mg/day is superior to treating them with aspirin 75mg/day. The main focus is on all-cause mortality (death rate) but data on morbidity (illnesses), symptoms, quality of life and on cardiovascular and renal function and anaemia will also be collected. A health economic analysis (to determine the relative cost benifits of the study to the healthcare of the patients within the trial) will be conducted if appropriate. Clearly, if no difference in outcomes is observed there is no value in a detailed health economic assessment. |
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| E.2.2 | Secondary objectives of the trial |
Secondary endpoints include
a)cardiovascular death or hospitalisation for heart failure (time to first event)
b)sudden death or a vascular event (myocardial infarction, stroke, peripheral embolism, requirement for angioplasty or vascular surgery) using a time to first event analysis
c)total days lost to death or hospitalisation (all causes)
d)quality-adjusted years alive (QALY)
e)cost per QALY.
Safety endpoints include hospitalisation for bleeding and deterioration in renal function or requirement for dialysis and the development of anaemia defined as the proportions of patients developing new-onset anaemia or with resolution of existing anaemia according to the W.H.O. definition and mean change in haemoglobin at 6 months. Serum creatinine and systolic blood pressure at 6 months are other safety outcomes. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
# Willing and able to provide written confirmation of informed consent
# A clinical diagnosis of heart failure
# Currently in sinus rhythm on clinical examination (supported by ECG evidence in previous year)
# Receiving diuretics for at least 6 weeks prior to inclusion
# Patients must have a telephone
# Patients must be willing to provide their personal contact details, their next of kin and those of their GP and hospital and local pharmacies to the national coordinating office and be willing to be contacted by telephone by these staff and be willing for the monitoring staff to contact their GP, hospital and pharmacies.
# Patients must be willing to have hospitalisation and other serious events tracked through mechanisms including, in England, the NHS Central Register (NHSCR) and the National Office of Statistics and, in Scotland, The Registrar General’s Office and NHS Information Statistics Division
Patients will be included regardless of aetiology (medical origins) of disease, since the great majority of patients with heart failure either have ischaemic heart disease as the primary cause or as a co-morbid condition.
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| E.4 | Principal exclusion criteria |
# Severe valve disease in the investigators opinion (an echocardiogram report within the previous 12 months must be available)
# Plasma NT-proBNP <400pg/ml (47.3pmol/L) or MR-proANP <200pmol/L (central lab)
# 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.
# Serum creatinine >250umol/L (local lab) - a measure of the health status of the kidneys.
# Intolerant of aspirin or clopidogrel or who have a contra-indication to such treatment or who require anti-coagulation will be excluded.
# Contraindications to aspirin or clopidogrel include
o Substantial, in the investigators opinion, bleeding from an uncorrected source within the previous year,
o Recent peptic ulcer disease
o History of haemorrhagic stroke,
o Known coagulation disorder (eg:- haemophilia)
o Full blood count suggesting iron deficiency (patients may be enrolled in the study after the cause of iron deficiency is investigated and treated) (local lab)
o Platelet count <100,000 (local lab) - a measure of the body's ability to clot blood
o Scheduled procedure that would require discontinuation of study medication for > 2 weeks (patient may be recruited after procedure)
o History of uncontrolled seizures or high risks of falls,
o Use of non-steroidal anti-inflammatory agents > 3 times a week
o Use of maintenance oral corticosteroids
o Women of child-bearing potential or who are breast feeding
o Patients with a history of asthma should not take part unless they have taken aspirin previously without ill-effect.
# Patients with an indication for oral anti-coagulation including
current or recent (within 12 months) atrial fibrillation or flutter (evidence of an ECG documenting sinus rhythm must be provided)
prior embolic stroke
mechanical prosthetic heart valve
# Patients requiring dual anti-platelet therapy are also excluded including patients within 3 months of an acute coronary syndrome, transient ischaemic attack or vascular procedure or within one year of receiving a drug eluting coronary stent.
# Patients likely to die of something other than heart failure or sudden (cardiac) death are excluded
# Inability to walk without the physical assistance of another person (patients with walking aids are permitted)
# Other patients deemed unlikely to comply with the protocol.
# Women who are at pregnant or who could become pregnant. Women of child-bearing age should be taking reliable contraception (tubal ligation or implanted contraceptive)
# Inability to communicate in English. Non-English speaking patients who have a friend or relative who can translate or who have other access to translation may participate.
# Patients who are unable to provide written informed consent
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| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 253 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The trial could end for three reasons:-
1. There is overwhelming benefit for one treatment. The trial will be closed immediately and when the data are verified patients & their doctors will be informed.
2. The planned futility analysis may indicate that the trial is not powered to show small differences. No further patients will be randomised. All patients will be followed until the last has completed 6 month.
3. The trials goes to planned completion after 1,200 deaths are verified. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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