A Randomized, Double-Blind Trial

Richard B. Alexander, MD; Kathleen J. Propert, ScD; Anthony J. Schaeffer, MD; J. Richard Landis, PhD; J. Curtis Nickel, MD; Michael P. O'Leary, MD; Michel A. Pontari, MD; Mary McNaughton-Collins, MD, MPH; Daniel A. Shoskes, MD; Craig V. Comiter, MD; Nand S. Datta, MD; Jackson E. Fowler, Jr, MD; Robert B. Nadler, MD; Scott I. Zeitlin, MD; Jill S. Knauss, MS; Yanlin Wang, MS; John W. Kusek, PhD; Leroy M. Nyberg, Jr, MD, PhD; and Mark S. Litwin, MD, MPH, and the Chronic Prostatitis Collaborative Research Network*

19 October 2004 | Volume 141 Issue 8| Pages 581-589

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is principally defined by pain in the pelvic region lasting more than 3 months. No cause of the disease has been established, and therapies are empirical and mostly untested. Antimicrobial agents and -adrenergic receptor blockers are frequently used.

Objective: To determine whether 6-week therapy with ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms in men with refractory, long-standing CP/CPPS.

Design: Randomized, double-blind trial with a 2 x 2 factorial design comparing 6 weeks of therapy with ciprofloxacin, tamsulosin, both drugs, or placebo.

Setting: Urology outpatient clinics at 10 tertiary care medical centers in North America.

Patients: Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment.

Measurements: The authors evaluated NIH-CPSI total score and subscores, patient-reported global response assessment, a generic measure of quality of life, and adverse events.

Interventions: Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily; a combination of the 2 drugs; or placebo.

Results: The NIH-CPSI total score decreased modestly in all treatment groups. No statistically significant difference in the primary outcome was seen for ciprofloxacin versus no ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments also did not differ significantly for any of the secondary outcomes.

Limitations: Treatment lasting longer than 6 weeks was not tested. Patients who had received less pretreatment may have responded differently.

Conclusion: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.

*For the members of the Chronic Prostatitis Collaborative Research Network, see the Appendix.

Editors' Notes

Context

Although the cause of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is unknown, physicians sometimes try to treat it with antibiotics or -receptor blockers.

Contribution

In this multicenter, double-blind factorial trial, 196 men with moderately severe CP/CPPS were randomly assigned to 6 weeks of treatment with ciprofloxacin, tamsulosin, both drugs, or placebo. Neither ciprofloxacin nor tamsulosin substantively reduced symptoms.

Implications

Ciprofloxacin and tamsulosin were not effective treatments for CP/CPPS.

Cautions

Patients had long-standing, refractory CP/CPPS and received trial treatments for only 6 weeks. Patients with new diagnoses who are given longer courses of the trial treatments might respond differently.

–The Editors

Author and Article Information

From Veterans Affairs Maryland Health Care System and University of Maryland School of Medicine, Baltimore, Maryland; University of Pennsylvania and Temple University, Philadelphia, Pennsylvania; Northwestern University, Chicago, Illinois; Queen's University, Kingston, Ontario, Canada; Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts; Cleveland Clinic Florida, Weston, Florida; University of Arizona, Tucson, Arizona; Charles Drew University and University of California, Los Angeles, California; University of Mississippi, Jackson, Mississippi; and the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.

Acknowledgments: The investigators are indebted to the patients who participated in this study.

Grant Support: By National Institutes of Health cooperative agreements U01 DK53572, U01 DK53730, U01 DK53736, U01 DK53734, U01 DK53732, U01 DK53746, and U01 DK53738. Boehringer Ingelheim provided tamsulosin and matching placebo; Bayer Corporation provided ciprofloxacin and matching placebo.

Potential Financial Conflicts of Interest: Consultancies: J.C. Nickel (Bayer, Boehringer Ingelheim), S.I. Zeitlin (Bayer); Honoraria: R.B. Alexander (Boehringer Ingelheim), J.C. Nickel (Bayer, Boehringer Ingelheim), D.A. Shoskes (Boehringer Ingelheim), S.I. Zeitlin (Bayer, Boehringer Ingelheim); Grants received: J.C. Nickel (Bayer, Boehringer Ingelheim); Other: S.I. Zeitlin (Bayer, Boehringer Ingelheim).

Requests for Single Reprints: Richard B. Alexander, MD, Urology (112), Veterans Affairs Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201; e-mail, ralexander@smail.umaryland.edu.

Current Author Addresses: Dr. Alexander: Urology (112), Veterans Affairs Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201.

Drs. Propert and Landis, Ms. Lang, and Ms. Knauss: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Blockley Hall 6th Floor, 423 Guardian Drive, Philadelphia, PA 19104.

Drs. Schaeffer and Nadler: Department of Urology—Tarry 16-703, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611.

Dr. Nickel: Department of Urology, Queen's University, Kingston General Hospital, Kingston, Ontario K7L2V7, Canada.

Dr. O'Leary: Brigham and Women's Hospital, 45 Francis Street, ASB11-3, Boston, MA 02115.

Dr. Pontari: Department of Urology, Temple University School of Medicine, 3401 North Broad Street, Philadelphia, PA 19140.

Dr. McNaughton-Collins: General Medicine Division, Massachusetts General Hospital, 50 Staniford Street, 9th Floor, Boston, MA 02114.

Dr. Shoskes: Department of Urology, Cleveland Clinic Florida, 2950 Cleveland Clinic Boulevard, Weston, FL 33331.

Dr. Comiter: University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724.

Dr. Datta: Martin Luther King Hospital, Charles Drew University, 12021 South Wilmington Avenue, Los Angeles, CA 90059.

Dr. Fowler: Department of Surgery, Division of Urology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216.

Dr. Zeitlin: University of California, Los Angeles, Department of Urology, 66-131 Center for the Health Sciences, Los Angeles, CA 90095.

Dr. Kusek: Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 2 Democracy Plaza, Room 617, 6707 Democracy Boulevard, Bethesda, MD 20892.

Dr. Nyberg: Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 2 Democracy Plaza, Room 627, 6707 Democracy Boulevard, Bethesda, MD 20892.

Dr. Litwin: University of California, Los Angeles, Department of Urology, 66-121 Center for the Health Sciences, Box 951738, Los Angeles, CA 90095.

Author Contributions: Conception and design R.B. Alexander, K.J. Propert, A.J. Schaeffer, J.R. Landis, J.C. Nickel, M.P. O'Leary, M.A. Ponteri, M. McNaughton-Collins, D.A. Shoskes, N.S. Datta, R.B. Nadler, S.I. Zeitlin, J.W. Kusek, L.M. Nyberg Jr., M.S. Litwin.

Analysis and interpretation of the data: R.B. Alexander, K.J. Propert, A.J. Schaeffer, J.R. Landis, J.C. Nickel, M.P. O'Leary, M. McNaughton-Collins, D.A. Shoskes, N.S. Datta, R.B. Nadler, S.I. Zeitlin, J.S. Knauss, Y. Wang, J.W. Kusek, M.S. Litwin.

Drafting of the article: R.B. Alexander, K.J. Propert, A.J. Schaeffer, J.C. Nickel, M.P. O'Leary, S.I. Zeitlin, J.W. Kusek, M.S. Litwin.

Critical revision of the article for important intellectual content: R.B. Alexander, K.J. Propert, A.J. Schaeffer, J.C. Nickel, M.P. O'Leary, M.A. Ponteri, M. McNaughton-Collins, D.A. Shoskes, R.B. Nadler, J.W. Kusek, M.S. Litwin.

Final approval of the article: R.B. Alexander, K.J. Propert, A.J. Schaeffer, J.R. Landis, J.C. Nickel, M.P. O'Leary, M.A. Ponteri, M. McNaughton-Collins, D.A. Shoskes, N.S. Datta, R.B. Nadler, L.M. Nyberg Jr., M.S. Litwin.

Provision of study materials or patients: R.B. Alexander, A.J. Schaeffer, J.C. Nickel, M.P. O'Leary, M.A. Ponteri, M. McNaughton-Collins, D.A. Shoskes, C.V. Comiter, N.S. Datta, J.E. Fowler Jr., R.B. Nadler, S.I. Zeitlin, M.S. Litwin.

Statistical expertise: K.J. Propert, J.R. Landis, J.S. Knauss, Y. Wang.

Obtaining of funding: A.J. Schaeffer, J.R. Landis, M.A. Ponteri, M. McNaughton-Collins, C.V. Comiter, J.W. Kusek, M.S. Litwin.

Administrative, technical, or logistic support: J.E. Fowler Jr., L.M. Nyberg Jr., M.S. Litwin.

Collection and assembly of data: R.B. Alexander, A.J. Schaeffer, J.C. Nickel, M.P. O'Leary, C.V. Comiter, R.B. Nadler, S.I. Zeitlin.