Trial Information

The Effect Of Aspirin On Survival Following Potentially Curative Resection Of Non Small Cell Carcinoma Of The Lung The Big A Trial

Study design Randomised study of aspirin 75mg to reduce the mortality in patients after
resection of non-small cell lung cancer. Patients already on aspirin, unsuitable for study
or not wishing to partake in this study will be asked for permission to be followed up via
their GP and the National Strategic Tracking service.

Methodology Initially all consultant thoracic and cardiothoracic surgeons in the UK will be
consulted to obtain permission for their patients to be included in this study. If they
agree the individual units' lung cancer nurses will actually be involved in recruiting post
operative patients into the study. We will use the lung cancer nurses to enter via a secure
electronic system patients pre operative characteristics and post operative staging and
histology. Mortality will followed via the strategic tracing service.

Study subjects/patients All patients undergoing potentially curative resection of non small
cell carcinoma of the lung. Patients will be recruited post operatively so that post
operative deaths are eliminated, and histology is known prior to randomisation.

Contamination of control limb

Patients in the aspirin limb will be asked at their 1 year, 3 years and 5 years out patient
appointment if they are still staking the aspirin. Patients in the control limb will be
asked at their 1 year, 3 years and 5 years out patient appointment if they have been started
on aspirin by anyone.

If these appointments are missed the patients GP will be contacted for this information, as
long as the patient has agreed for us to contact their GP.

Data collection This will be prospective via a secure web server, hosted on an NHS computer
located in a secure NHS IT locked room.

Study procedures No invasive procedure, samples or tissues will be performed or obtained in
any patients.

Study intervention Aspirin 75 mg/day or no tablet taken for a period of 5 years after
randomisation.

Reducing adverse events

All patients will be assessed by the researcher to eliminated patients with as history of
gastric or duodenal ulcers, or known allergy to aspirin or other NSAIDs.

Monitoring of Adverse events All patients will be given a business card with a contact
number, an email address and a web address so that they can report all adverse events while
participating in this trial. In addition all general practitioners with patients in the
trial will be notified.

Specific adverse events we will be following include:

Stopping trial medication secondary to side effects, GI bleeds, stomach ulcers, anaemia that
require hospital admission and Blood transfusion(s)

Data Monitoring Committee The data management committee will analyse survival data in the
control and intervention limb every 6 months up to 5 years with regard to mortality and
gastrointestinal side effects that required hospital admission.

If the mortality in the aspirin treatment group exceeds more than 3 Standard deviations
above the control mortality rate the trial will be stopped immediately and the aspirin users
all contacted immediately and informed to stop the aspirin immediately.

The gastrointestinal side effects of aspirin have been widely studied and as aspirin is an
over the counter product being used in its lowest dose formulation we do not aim to use
gastrointestinal side effects as a marker for stopping the trial.

GP contacts All GPs will be informed of their patients inclusion in this trial.

Statistical analysis. This will be performed by Dr Mark Jackson or a delegated member of his
team, at Liverpool Heart and Chest Hospital.

Sample size Based on a retrospective trail conducted in Liverpool Heart and Chest hospital.
Accepting the suggested hazard ratio of 0.84 and a difference in 5-year survival of
approximately 6%, various power calculations were performed to derive an estimate of the
sample size required for such a trial. Depending on the aspirin:non-aspirin ratio and based
on standard assumptions, a combined total of between 2000 and 3000 patients would need to be
recruited to detect a significant difference in survival. Hence we aim to recruit 2,500
patients.