Betsy Morrill

The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study

BACKGROUND Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement. OBJECTIVE To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression over 4 yr in men at increased risk of progression. DESIGN, SETTING, AND PARTICIPANTS The Combination of Avodart and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men > or =50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score > or =12, prostate volume > or =30 cm(3), prostate-specific antigen 1.5-10 ng/ml, and maximum urinary flow rate (Q(max)) >5 and < or =15 ml/s with minimum voided volume > or =125 ml. INTERVENTION Oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. MEASUREMENTS The 4-yr primary end point was time to first AUR or BPH-related surgery. Secondary end points included BPH clinical progression, symptoms, Q(max), prostate volume, safety, and tolerability. RESULTS AND LIMITATIONS Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery. Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression. Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of an imbalance in the composite term of cardiac failure among the three study arms. The lack of placebo control is a study limitation. CONCLUSIONS The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement. CLINICALTRIALS.GOV IDENTIFIER: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).

Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS)

Study Type – Therapy (RCT)

Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride.

The relationship between 5α‐reductase inhibitors and blood loss from the prostate has been well described and investigated previously. In a well‐conducted study, authors from Sweden show that dutasteride, despite significantly lowering the tissue dihydrotestosterone levels, did not lower blood loss or transfusion rates after TURP.

Effect of dutasteride, tamsulosin and the combination on patient‐reported quality of life and treatment satisfaction in men with moderate‐to‐severe benign prostatic hyperplasia: 2‐year data from the CombAT trial

To investigate the effect of dutasteride and tamsulosin as combined therapy compared with each monotherapy for improving patient‐reported health outcomes in men with moderate‐to‐severe urinary symptoms and prostate enlargement, reporting the pre‐planned 2‐year analyses from the CombAT trial.

Ranitidine versus cimetidine in the healing of erosive esophagitis

Ranitidine 150 mg twice daily (BID) is an approved therapeutic approach for relieving the symptoms of gastroesophageal reflux disease. Ranitidine 150 mg four times daily (QID) and cimetidine 800 mg BID are indicated for endoscopically diagnosed erosive esophagitis. This 12-week, randomized, multicenter trial involving 696 patients compared ranitidine 150 mg BID and ranitidine 150 mg QID with cimetidine 800 mg BID in healing erosive esophagitis. Healing rates, as determined by endoscopy, at 4, 8, and 12 weeks were comparable with ranitidine 150 mg BID (38%, 56%, and 71%, respectively) and cimetidine 800 mg BID (37%, 52%, and 68%, respectively), as were reductions in heartburn frequency and antacid consumption. However, ranitidine 150 mg QID produced significantly higher healing rates (49%, 67%, and 77%, respectively) and greater reductions in heartburn frequency and antacid consumption than cimetidine 800 mg BID. All treatment regimens were well tolerated. Thus ranitidine 150 mg BID is as effective as cimetidine 800 mg BID, and ranitidine 150 mg QID is more effective than cimetidine 800 mg BID in healing erosive esophagitis and reducing heartburn frequency and antacid consumption.

Corrigendum to “The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study” [Eur Urol 2010;57:123–31]

Department of Urology, UT Southwestern Medical Center, Dallas, Texas, USA Deaconess Clinic, Evansville, Indiana, USA Department of Urology, University of Toronto, Toronto, Ontario, Canada Urology Department, State University of Rio de Janeiro, Rio de Janeiro, Brazil Research and Development, GlaxoSmithKline, Research Triangle Park, North Carolina, USA Department of Urology, Universita Vita Salute San Raffaele, Milan, Italy

The psychometric validation of a US English satisfaction measure for patients with benign prostatic hyperplasia and lower urinary tract symptoms

BackgroundThe purpose of the current study was to validate the US English Patient Perception of Study Medication (PPSM) questionnaire, which measures patient satisfaction with Benign Prostatic Hyperplasia (BPH) treatment and was administered to men with BPH lower urinary tract symptoms (LUTS) enrolled in a multi-national clinical trial.MethodsPatients with moderate to severe BPH symptoms completed three disease-specific measures: The International Prostate Symptom Score (IPSS), the BPH Impact Index (BII) and the PPSM, at baseline (after completion of the placebo run-in period) and at every 13-week clinic visit thereafter for the duration of the study treatment period. The PPSM was analysed to assess its variability, reliability and validity.ResultsThere were 879 patients included in the analyses, with a mean age of 66.7 years. The PPSM was found to comprise two factors – PPSM-Global and PPSM-Pain, with a Total Score ranging from 7 to 49. It demonstrated good internal consistency (Cronbachs alpha ranged from .95 to .97) and also demonstrated convergent validity through significant correlations with the IPSS (.48 to .58), IPSS Quality of Life (QoL) item (.41 to .63) and BII (.31 to .45) and known-groups validity against the IPSS, IPSS QoL item and BII.ConclusionResults support the use of the PPSM as a measure of satisfaction in BPH patient groups.

Ranitidine 300 mg twice daily and 150 mg four-times daily are effective in healing erosive oesophagitis.

BACKGROUND: Ranitidine 150 mg q.d.s. is the currently recommended dosage in the United States for the treatment of erosive oesophagitis. To determine whether a higher dose of ranitidine administered less frequently would also be effective in healing erosive oesophagitis, we compared ranitidine 300 mg b.d. with ranitidine 150 mg q.d.s. in the treatment of erosive oesophagitis. METHODS: This multicentre, double‐ blind, randomized, placebo‐controlled study conducted in the United States compared two dosages of ranitidine in 772 patients with endoscopically diagnosed erosive oesophagitis. Patients were treated with ranitidine 300 mg b.d., ranitidine 150 mg q.d.s. or placebo for up to 12 weeks. Endoscopies were repeated after 4, 8 and 12 weeks of treatment. RESULTS: Ranitidine 300 mg b.d. was significantly more effective than placebo in healing erosive oesophagitis at weeks 8 and 12 (51 vs. 36% and 66 vs. 52%, respectively; P < or = 0.004). Significantly higher healing rates were also achieved with ranitidine 150 mg q.d.s. compared with placebo at 4, 8 and 12 weeks (37 vs. 21%, 62 vs. 36% and 77 vs. 52%, respectively; P < 0.001). Healing rates were significantly higher with ranitidine 150 mg q.d.s. than with ranitidine 300 mg b.d. at all scheduled endoscopies (P < or = 0.041). CONCLUSIONS: Ranitidine 300 mg b.d. is effective in healing erosive oesophagitis and may be appropriate as an alternative dosage regimen to ranitidine 150 mg q.d.s. in some patients with erosive oesophagitis.

The effects of combination therapy with dutasteride plus tamsulosin on clinical outcomes in men with symptomatic BPH: 4-year post hoc analysis of European men in the CombAT study.

CombAT (Combination of Avodart and Tamsulosin) was a randomised, double-blind study in men (n=4844) aged ⩾50 years with a clinical diagnosis of BPH. Patients were randomised to daily tamsulosin 0.4 mg, dutasteride 0.5 mg or both for 4 years. The primary endpoint was time to acute urinary retention (AUR) or BPH-related surgery. Secondary endpoints included BPH clinical progression, symptoms and maximum urinary flow rate. A post hoc analysis of data from the European subgroup was conducted. A total of 2925 men were randomised to treatment in Europe as part of CombAT (tamsulosin, n=972; dutasteride, n=970; combination, n=983). Combination therapy significantly reduced the relative risk of AUR or BPH-related surgery compared with either monotherapy at 4 years, and also significantly reduced the risk of BPH clinical progression. Combination therapy also provided significantly greater symptom improvement than either monotherapy at 4 years. Safety and tolerability of dutasteride plus tamsulosin was consistent with previous experience of this combination and with the monotherapies. These data provide further evidence to support the use of long-term combination therapy (dutasteride plus tamsulosin) in men with moderate-to-severe lower urinary tract symptoms because of BPH and prostatic enlargement. The results in the European subgroup are generally consistent with those in the overall study population.