Trial design
The diabetic postoperative mortality and morbidity (DIPOM) trial: rationale and design of a multicenter, randomized, placebo-controlled, clinical trial of metoprolol for patients with diabetes mellitus who are undergoing major noncardiac surgery

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Abstract

Background

Recent trials suggest that perioperative β-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery. Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality. They may, therefore, benefit from perioperative β-blockade.

Methods

The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial is an investigator-initiated and -controlled, centrally randomized, double-blind, placebo-controlled, multicenter trial. We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were β-blocker naive, ≥40 years old, and undergoing noncardiac surgery. The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery. The primary outcome measure is the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization. Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public databases. The study was powered on the basis of an estimated 30% 1-year event rate in the placebo arm and a 33% relative risk reduction in the metoprolol arm. The median follow-up period was 18 months.

Results

Enrollment started in July 2000 and ended in June 2002. A total of 921 patients were randomized, and 54% of these patients had known cardiac disease, hypertension, or both.

Conclusion

The results of this study may have implications for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery.

Section snippets

Trial design

The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial is a randomized, double-blind, placebo-controlled, multicenter trial, launched on July 1, 2000. Randomization was completed on June 30, 2002 with 921 patients included. The primary aim of the trial was to assess the long-term effect of 7-day perioperative β-blockade on perioperative and postoperative mortality and cardiac morbidity in patients with diabetes mellitus who were undergoing major noncardiac surgery.

Current status of the trial

From July 2000 to January 2002 (the scheduled period of recruitment), 725 patients were enrolled. The average monthly recruitment for the entire study was 43 patients/month. The DIPOM Steering Committee decided to extend the period of recruitment by 6 months. The last patient was randomized on July 1, 2002. A total of 2066 candidate patients were identified in the 13 centers (Figure 1), and, of these, 921 patients (45%) were randomized (Table III). Baseline characteristics of the randomized

Design features

The design of the DIPOM trial differs from that of previous perioperative β-blocker trials. First, it is a large multicenter trial with increased power to measure outcomes after a minimum of 6 months (median, 18 months) of follow-up. In-hospital outcomes and outcomes at 30 days will also be reported. Second, only patients who were β-blocker naive were included, because β-blocker withdrawal may increase the risk of postoperative cardiovascular morbidity and mortality.34 Third, patients with

Conclusion

DIPOM is, according to our knowledge, the first trial examining the effects of perioperative β-blocker administration on outcomes, including mortality and cardiac morbidity, in patients with diabetes mellitus. The results of the study may have implications for therapeutic measures in a growing and threatened patient population. If the trial shows that perioperative β-blockade reduces postoperative mortality and morbidity rates in patients with diabetes mellitus, this will be an important

Acknowledgements

We thank the patients who participated in the DIPOM trial, the surgeons at the surgical departments for their excellent collaboration, AstraZeneca for helpful discussions and excellent collaboration during the design and inclusion phase of the DIPOM trial and for free supply of the study drug, and AstraZeneca, the Danish Heart Foundation, the Danish Diabetes Foundation, the Copenhagen Hospital Corporation's Research Council, and the Danish Medical Research Council's “Program for Strengthening

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    *See Appendix for list of DIPOM Group members.

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