📃 Paper Title: 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
🧍 Author: CG Roehrborn
🕒 Year: 2009
📚 Journal: European Urology
🌎 Country: USA
ㅤContext to the study:
Can you tell me about a study that demonstrated the superiority of combination therapy (dutasteride + tamsulosin) over monotherapy for treating men with symptomatic benign prostatic hyperplasia (BPH)?
ㅤ✅ Take-home message of study:
The occurrence of drug-related adverse events was significantly greater in the combination group, primarily due to the increased incidence of ejaculatory disorders. But no significant difference in withdrawal rates due to adverse events.
ㅤ Multinational, multicentre, randomised, double-blind, parallel-group study
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Study participants:
Number included: 4844
Inclusion criteria:
Male
Age ≥50 yrs
Patients with a clinical diagnosis of benign prostatic hyperplasia (BPH) by medical history and physical examination
Patients with an International Prostate Symptom Score (IPSS) ≥ 12 points
Patients with a prostate volume ≥ 30 cm3 by transrectal ultrasound (TRUS)
Patients with a total serum prostate-specific antigen (PSA) between 1.5 - 10 ng/ml
Patients with a maximum urinary flow rate (Qmax) > 5 and ≤ 15 ml/s with minimum voided volume ≥ 125 ml
Exclusion criteria:
History or evidence of prostate cancer, previous prostate surgery
Acute urinary retention (AUR) within 3 months prior to study entry
Use of 5α-reductase inhibitor (5-ARI) within 6 months (or Dutasteride within 12 months) prior to study entry
Use of an α-blocker or phytotherapy for BPH within 2 weeks prior to study entry
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Key study outcomes:
Mean follow-up: 3195 (66%) completed the 48 month visit.
Primary endpoints
4-yr incidence of AUR or BPH-related surgery:
combination therapy: 4.2% (2.2% AUR, 2.4% BPH-related surgery)
dutasteride: 5.2% (2.7% AUR, 3.5% BPH-related surgery) (combination vs dutasteride: p = 0.18)
tamsulosin: 11.9% (6.8% AUR, 7.8% BPH-related surgery) (combination vs tamsulosin: p < 0.001)
Combination therapy reduced the relative risk (RR) of AUR or BPH-related surgery by 65.8% compared with tamsulosin and 19.6% compared with dutasteride.
Secondary endpoints
4-yr incidence of BPH clinical progression (symptom deterioration by IPSS ≥ 4 points, BPH-related AUR, BPH-related urinary incontinence, BPH-related urinary tract infection or urosepsis, BPH-related renal insufficiency, BPH-related surgery, AUR):
combination therapy: 12.6%
dutasteride: 17.8% (p<0.001)
tamsulosin: 21.5% (p<0.001)
Combination therapy reduced the RR of BPH clinical progression by 44.1% compared with tamsulosin and 31.2% compared with dutasteride.
The proportion of men with a ≥ 3-point IPSS improvement:
combination - 71%
tamsulosin - 59% (p<0.01)
dutasteride - 66% (p<0.01)
The adjusted mean increases in Qmax from baseline:
combination - 2.4 ml/s
tamsulosin - 0.7 ml/s (p<0.001)
dutasteride - 2.0 ml/s (p = 0.05)
The adjusted mean percentage change from baseline in total prostate volume:
Combination - -27.3%
Tamsulosin - +4.6%
Dutasteride - -28.0%
Serum PSA from baseline:
Combination - decreased by a median of 57.1%
Dutasteride - decreased by a median of 56.0%
Tamsulosin - increased by a median of 18.4%
Safety / Tolerability:
The occurrence of drug-related adverse events was significantly greater in the combination group, but no significant difference in withdrawal rates due to adverse events.
This increase was driven by an increased incidence of ejaculatory disorders.
There were no reports of "floppy iris syndrome" or malignant breast tumors in any treatment group.
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Study Limitations:
GlaxoSmithKline, the manufacturer of dutasteride and tamsulosin, sponsored the study, which could introduce bias.
The study population was limited to men with moderate-to-severe symptoms of BPH and prostate volume ≥ 30 cc, so the results may not be generalizable to men with milder symptoms or smaller prostate volumes.
The study was limited to a 4-year follow-up period, so longer-term effects of combination therapy could not be evaluated.
The absence of a placebo arm due to ethical reasons may be a limitation because all patients were aware they were receiving active therapy.
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