Skip to main content
SpringerLink
Log in

Data Monitoring in the Prospective Randomized Milrinone Survival Evaluation: Dealing With an Agonizing Trend

  • Chapter
Data Monitoring in Clinical Trials

  • 1312 Accesses

Abstract

The Prospective Randomized Milrinone Survival Evaluation (PROMISE) was conducted to clarify discordant findings in previous experimental and clinical studies with milrinone, a cyclic AMP-enhancing positive inotropic agent. Earlier studies had shown positive effects of milrinone on cardiac function and exercise performance in patients with chronic heart failure. To determine the effect of milrinone on mortality, patients with severe chronic heart failure who remained symptomatic despite conventional therapy were randomized to receive either active drug or a matching placebo. The trial was terminated after 20 months, before its scheduled completion, based on an observed adverse effect of milrinone on survival. This paper describes the experience of the Data Monitoring and Safety Monitoring Board (DSMB) in dealing with an emerging negative trend in survival when there were other known beneficial effects of the drug.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Packer M. 1988. Vasodilator and inotropic drugs for chronic heart failure: distinguishing hype from hope. Am J Cardiol 12:1299–1317.

    Article  MathSciNet  Google Scholar 

  2. Feldman MD, Copelas L, Gwanthmey JK, et al. 1987. Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. Circulation 75:331–339.

    Article  Google Scholar 

  3. Wilmshurst PT, Walker Jm, Fry CH, et al. 1984. Inotropic and vasodilator effects of amrinone on isolated human tissue. Cardiovasc Res 18:302–309.

    Article  Google Scholar 

  4. Jain P, Brown EJ Jr, Langenback EG, et al. 1991. Effects of milrinone on left ventricular remodeling after acute myocardial infarction. Circulation 84:796–804.

    Google Scholar 

  5. Sweet CS, Ludden CT, Stabilito II, Emmert SE, Heyse JF. 1988. Beneficial effects of milrinone and enalapril on long-term survival of rats with healed myocardial infarction. Eur J Pharmacol 147:29–37.

    Article  Google Scholar 

  6. Packer M, Leier CV. 1987. Survival in congestive heart failure during treatment with drugs with positive inotropic actions. Circulation 75:Suppl IV:IV-55–IV-63.

    Google Scholar 

  7. DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. 1989. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients wiht chronic heart failure. N Engl J Med 320:677–683.

    Article  Google Scholar 

  8. Baim DS, McDowell AV, Cherniles J, et al. 1983. Evaluation of a new bipyridine inotropic agent—milrinone—in patients with severe congestive heart failure. N Engl J Med 309:748–756.

    Article  Google Scholar 

  9. Simonton CA, Chatterjee K, Cody RJ, et al. 1985. Milrinone in congestive heart failure: acute and chronic hemodynamic and clinical evaluation. J Am Coll Cardiol 6:453–459.

    Article  Google Scholar 

  10. Chesebro JH, Browne KF, Fenster PE, Garland WT, Konstam MA. 1988. The hemodynamic effects of chronic oral milrinone therapy: a multicenter controlled trial. J Am Coll Cardiol 11:144A. abstract

    Google Scholar 

  11. Packer M. 1989. Effect of phosphodiesterase inhibitors on the survival of patients with chronic congestive heart failure. Am J Cardiol 63:41A–45A.

    Article  Google Scholar 

  12. Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, et al. 1991. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 325:1468–1475.

    Article  Google Scholar 

  13. Fisher MM, Roecker EB, DeMets D. 2001. The role of an independent statistical analysis center in the industry-modified National Institutes of Health model. Drug Information Journal 35:115–129.

    Article  Google Scholar 

  14. Lan KKG, DeMets DL. 1983. Discrete sequential boundaries for clinical trials. Biometrika 70:659–663.

    Article  MathSciNet  MATH  Google Scholar 

  15. O’Brien PC, Fleming TR. 1979. A multiple testing procedure for clinical trials. Biometrics 35:549–556.

    Article  Google Scholar 

  16. DeMets DL, Pocock S, Julian DG: 1999. The agonising negative trend in monitoring clinical trials. Lancet 354:1983–1988.

    Article  Google Scholar 

  17. US Food and Drug Administration (2001) Draft Guidance for Clinical Trial sponsors on the establishment and operation of Clinical Trial Data Monitoring Committees. Rockville, MD: FDA. http://www.fda.gov/cber/gdlns/clindatmon.htm

    Google Scholar 

  18. Ellenberg S, Fleming T, DeMets D. 2002. Data Monitoring Committees in Clinical Trials: A Practical Perspective. John Wiley & Sons, Ltd., West Sussex, England.

    Book  Google Scholar 

  19. Canner PL. 1983. Monitoring of the data for evidence of adverse or beneficial treatment effects. Control Clin Trials 4:467–483.

    Article  Google Scholar 

  20. Friedman LM, Furberg CD, DeMets DL. 1998. Fundamentals of Clinical Trials. Third Edition, Springer-Verlag, New York.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin

    Susan Anderson

  2. Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan

    Robert Cody

  3. Center for Biostatistics and Clinical Science, University of Texas Southwestern Medical Center, Dallas, Texas

    Milton Packer

  4. CV Ventures, LLC, Blue Bell, Pennsylvania

    Richard Schwarz

Authors
  1. Susan Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Cody
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Milton Packer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biostatistics and Medical Informatics, University of Wisconsin Medical School, Madison, WI, 53972-4675, USA

    David L. DeMets

  2. Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Curt D. Furberg

  3. Bethesda, MD, USA

    Lawrence M. Friedman

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer Science+Business Media, Inc.

About this chapter

Cite this chapter

Anderson, S., Cody, R., Packer, M., Schwarz, R. (2006). Data Monitoring in the Prospective Randomized Milrinone Survival Evaluation: Dealing With an Agonizing Trend. In: DeMets, D.L., Furberg, C.D., Friedman, L.M. (eds) Data Monitoring in Clinical Trials. Springer, New York, NY. https://doi.org/10.1007/0-387-30107-0_19

Download citation

Publish with us

Policies and ethics

Search

Navigation