Randomised control trial

Hawkey GM, Cole AT, McIntyre AS et al
Drug treatments in upper gastrointestinal bleeding: value of endoscopic findings as surrogate end points.
Gut
2002; 49: 372-379

Submitted by:Anna Morgan - ST6 Emergency Medicine
Institution:Homerton Hospital
Date submitted:19th May 2011

Before CA, i rated this paper: 5/10

1 Objectives and hypotheses

1.1 Are the objectives of the study clearly stated?

Yes, it had two objectives, the first was to evaluate whether blood in the stomach at endoscopy was sufficiently predictive of clinically important outcomes to be considered as a surrogate end point. The second was to investigate the effect of lansoprazole and tranexamic acid on this and other endoscopic findings.

2 Design

2.1 Is the study design suitable for the objectives

Yes

2.2 Who / what was studied?

414 patients who presented to UK hospitals with a presumed upper gastrointestinal bleed. Patients were randomised to receive either lansoprazole, tranexamic acid, lansoprazole and tranexamic acid or placebo.

2.3 Was this the right sample to answer the objectives?

Yes

2.4 Is the study large enough to achieve its objectives? Have sample size estimates been performed?

A sample size was calculated. The trial has sufficient numbers to achieve its objectives, which were to evaluate whether the endoscopic finding of blood in the stomach could be used as a surrogate end point and to investigate the effect of lansoprazole and tranexamic acid on this end point. It does not have sufficient numbers to allow analysis of differences in clinical endpoints for patients given lansoprazole and tranexamic acid.

2.5 Were all subjects accounted for?

Yes

2.6 Were all appropriate outcomes considered?

Yes

2.7 Has ethical approval been obtained if appropriate?

Unclear

2.8 Were the patients randomised between treatments?

Yes

2.9 How was randomisation carried out?

In blocks of four.

2.10 Are the outcomes clinically relevant?

The finding of the paper suggest that the amount of blood in stomach is correlated with the clinically relevant outcomes of rebleeding rates and surgery.

3 Measurement and observation

3.1 Is it clear what was measured, how it was measured and what the outcomes were?

Yes

3.2 Are the measurements valid?

Yes

3.3 Are the measurements reliable?

The measurement of amount of blood in the stomach and other endoscopic endpoints are to some degree subjective. No measurement of interoperator agreement is provided with this study

3.4 Are the measurements reproducible?

See above

3.5 Were the patients and the investigators blinded?

Yes

4 Presentation of results

4.1 Are the basic data adequately described?

Yes

4.2 Were groups comparable at baseline?

Yes

4.3 Are the results presented clearly, objectively and in sufficient detail to enable readers to make their own judgement?

Yes

4.4 Are the results internally consistent, i.e. do the numbers add up properly?

Yes

4.5 Were side effects reported?

Briefly, but more detail would have been helpful.

5 Analysis

5.1 Are the data suitable for analysis?

Yes

5.2 Are the methods appropriate to the data?

Yes

5.3 Are any statistics correctly performed and interpreted?

Yes

6 Discussion

6.1 Are the results discussed in relation to existing knowledge on the subject and study objectives?

Yes

6.2 Is the discussion biased?

7 Interpretation

7.1 Are the authors' conclusions justified by the data?

Yes, the paper concludes that the measurement of blood in the stomach is predictive of clinically important outcomes and that the use of tranexamic acid and of lansoprazole reduce the amount of blood found at endoscopy. No evidence of synergy between the two drugs was found.

7.2 What level of evidence has this paper presented? (using CEBM levels)

7.3 Does this paper help me answer my problem?

Yes, it suggests that using tranexamic acid reduces the amount of blood found at endoscopy in patients with an upper gastrointestinal bleed and that it may therefore improve outcomes in patients with upper gastrointestinal bleeds. Lansoprazole had a similar effect but no synergy was demonstrated when the two drugs were used together. On the basis of the findings of this paper there would not appear to be any benefit to using tranexamic acid and a proton pump inhibitor together compared to using a single agent.

After CA, i rated this paper: 7/10

8 Implementation

8.1 Can any necessary change be implemented in practice?

The findings of the paper would not cause me to change my practice at present.

8.2 What aids to implementation exist?

8.3 What barriers to implementation exist?