CombAT: Dutasteride, Tamsulosin or Both for Symptomatic BPH With Prostatic Enlargement

Bottom line Mixed

Over 4 years, dutasteride plus tamsulosin lowered acute urinary retention or BPH surgery versus tamsulosin (4.2% versus 11.9%) but not significantly versus dutasteride alone (5.2%) in men with prostates of 30 mL or more, and improved symptoms more than either drug.

Combination beat tamsulosin but not dutasteride on AUR or surgery; symptoms improved most with combination.

CombAT (Combination of Avodart and Tamsulosin) was a multicenter, double-blind, parallel-group randomized trial of dutasteride plus tamsulosin versus either drug alone in 4,844 men with symptomatic BPH, a prostate of 30 mL or more and PSA 1.5 to 10 ng/mL, with time to first acute urinary retention (AUR) or BPH-related surgery over 4 years as the clinical-outcome primary endpoint.^[1] Combination therapy reduced that endpoint versus tamsulosin (4.2% versus 11.9%; relative risk 0.34, 95% CI 0.26 to 0.45) but not significantly versus dutasteride alone (5.2%; 0.80, 95% CI 0.58 to 1.11).^[1][2]

Design and population

Multicenter, double-blind, parallel-group randomized trial. 4,844 men aged 50 or older with moderate-to-severe LUTS (IPSS 12 or higher), prostate volume 30 mL or more and PSA 1.5 to 10 ng/mL.

Arms

Dutasteride 0.5 mg plus tamsulosin 0.4 mg daily versus dutasteride 0.5 mg daily alone versus tamsulosin 0.4 mg daily alone

Report and follow-up

2010 · 4 years of double-blind treatment

Endpoint	Results	Effect	Finding
4-year AUR or BPH-related surgery, combination versus tamsulosin	67/1,610 (4.2%) vs 191/1,611 (11.9%)	RR 0.34; CI 0.26–0.45; P <0.001	Met
4-year AUR or BPH-related surgery, combination versus dutasteride	67/1,610 (4.2%) vs 84/1,623 (5.2%)	RR 0.8; CI 0.58–1.11; P 0.18	Not met
4-year AUR and BPH-related surgery with the first occurrence of each event counted separately	AUR 36 (2.2%); surgery 38 (2.4%) vs AUR 44 (2.7%); surgery 56 (3.5%) vs AUR 109 (6.8%); surgery 126 (7.8%)	—	Descriptive
4-year first BPH clinical progression event	203/1,610 (12.6%) vs 289/1,623 (17.8%) vs 347/1,611 (21.5%)	—	Met
48-month change in IPSS, combination versus tamsulosin	-6.3 points vs -3.8 points	difference -2.5; CI -2.96–-2.07; P <0.001	Met
48-month change in IPSS, combination versus dutasteride	-6.3 points vs -5.3 points	difference -0.96; CI -1.4–-0.52; P <0.001	Met

Harms: Ejaculation disorders: 11% vs 2% vs 4%; Erectile dysfunction (any cause): 167/1,610 (10.4%) vs 147/1,623 (9.1%) vs 109/1,611 (6.8%); Composite cardiac failure: 12/1,610 (0.7%) vs 2/1,623 (0.1%) vs 9/1,611 (0.6%)

NCT00090103 · Report DOI

Design

Men were 50 or older with a clinical diagnosis of BPH, an IPSS of 12 or more, a transrectal-ultrasound prostate volume of 30 mL or more, serum PSA 1.5 to 10 ng/mL, Qmax above 5 and up to 15 mL/s, and a voided volume of at least 125 mL.^[1] Prostate cancer and previous prostatic surgery were exclusion criteria. A 4-week single-blind placebo run-in preceded randomization to dutasteride 0.5 mg, tamsulosin 0.4 mg or both once daily, with matching placebos, for 4 years.^[1][2] About 52% of the men had earlier exposure to a 5-alpha-reductase inhibitor (5-ARI) or an alpha-blocker.^[3]

The protocol set two separate primary endpoints: change in IPSS at 2 years and time to first AUR or BPH-related surgery at 4 years.^[4][5] BPH clinical progression was a secondary endpoint defined as IPSS deterioration of 4 points or more on two consecutive visits, AUR, BPH-related incontinence, recurrent BPH-related urinary tract infection or BPH-related renal insufficiency.^[2] Qmax and prostate volume were also secondary endpoints.^[3]

Results

AUR or BPH-related surgery occurred in 67/1,610 men (4.2%) on combination therapy, 84/1,623 (5.2%) on dutasteride and 191/1,611 (11.9%) on tamsulosin.^[1][2] The relative risk versus tamsulosin was 0.34 (95% CI 0.26 to 0.45; log-rank P < 0.001); versus dutasteride it was 0.80 (95% CI 0.58 to 1.11; P = 0.18), so the difference versus dutasteride was not significant.^[1][2] Counting the first occurrence of each event separately, AUR occurred in 36 (2.2%), 44 (2.7%) and 109 (6.8%) men and BPH-related surgery in 38 (2.4%), 56 (3.5%) and 126 (7.8%), respectively.^[1]

A first BPH clinical progression event occurred in 203/1,610 men (12.6%) on combination therapy, 289/1,623 (17.8%) on dutasteride and 347/1,611 (21.5%) on tamsulosin; the report states combination therapy was significantly superior to both monotherapies.^[1][2]

At the 2-year primary time point, the adjusted mean IPSS change was -6.2 points with combination therapy, -4.9 with dutasteride and -4.3 with tamsulosin.^[5][3] The differences were -1.3 points versus dutasteride (95% CI -1.69 to -0.86) and -1.8 versus tamsulosin (95% CI -2.23 to -1.40), both P < 0.001; the advantage over dutasteride began at month 3 and over tamsulosin at month 9.^[3][5] At 4 years the changes were -6.3, -5.3 and -3.8 points, with differences of -0.96 (95% CI -1.40 to -0.52) versus dutasteride and -2.5 (95% CI -2.96 to -2.07) versus tamsulosin, both P < 0.001.^[2][3] The AUA guideline's review of the trial describes no clinically important difference in symptoms or quality of life between combination therapy and dutasteride alone.^[6]

Qmax rose by 2.4, 1.9 and 0.9 mL/s at 24 months and by 2.4, 2.0 and 0.7 mL/s at 48 months; the label states that the additional improvement over dutasteride was no longer significant at month 48.^[2][3] Prostate volume at 48 months changed by -27.3% with combination therapy, -28.0% with dutasteride and +4.6% with tamsulosin.^[3]

In post hoc baseline-subgroup analyses, combination therapy lowered AUR or BPH-related surgery versus tamsulosin in men with baseline prostate volume above 42 mL, in every PSA subgroup and in all other subgroups analyzed.^[7] In a separate analysis of 4-year IPSS storage and voiding subscores, combination therapy was better than dutasteride in men with a baseline prostate volume of 30 to under 58 mL but not at 58 mL or more.^[8]

Surgery and treatment delivery

BPH-related surgery was a component of the primary endpoint: 38 men on combination therapy, 56 on dutasteride and 126 on tamsulosin had a first BPH-related operation during the 4 years.^[1]

Baseline mean age was 66 years, mean IPSS about 16.4, mean prostate volume about 55 mL and mean Qmax about 10.7 mL/s; 88% of the men were white.^[3] Four years of double-blind treatment were completed by 1,113/1,610 men (69.1%) on combination therapy, 1,093/1,623 (67.3%) on dutasteride and 989/1,611 (61.4%) on tamsulosin; adverse events led 211 (13.1%), 185 (11.4%) and 210 (13.0%) to stop.^[2]

Adverse events

Ejaculation disorders were reported by 11% on combination therapy, 2% on dutasteride and 4% on tamsulosin; the incidence with combination therapy was 7.8% in the first 6 months and fell to 1.6% in months 7 to 12.^[3] The label notes that these sexual adverse reactions may persist after treatment stops.^[3] Erectile dysfunction of any cause was reported by 167/1,610 (10.4%), 147/1,623 (9.1%) and 109/1,611 (6.8%).^[2]

The composite term cardiac failure occurred in 12/1,610 men (0.7%) on combination therapy, 2/1,623 (0.1%) on dutasteride and 9/1,611 (0.6%) on tamsulosin; the label states that the clinical significance of the imbalance is unknown and that no causal relationship has been established.^[3] Serious adverse events occurred in 303 (18.8%), 339 (20.9%) and 348 (21.6%).^[2] Withdrawal because of adverse reactions was 6% with combination therapy and 4% in each monotherapy arm, with erectile dysfunction the leading reason in every arm.^[3]

Limitations

There was no placebo arm, so the absolute effect of each drug against no treatment cannot be derived from the trial.^[1] Completion of 4 years of treatment differed by arm (69%, 67% and 61%).^[2] The sponsor was GlaxoSmithKline.^[2]

In conversation

• Builds on MTOPS (2003). Designed after MTOPS to test dutasteride plus tamsulosin in men with larger prostates and higher PSA, without a placebo arm.

MTOPS randomized 3,047 men with an IPSS of 8 or more to placebo, doxazosin, finasteride or both; combination therapy gave better clinical outcomes than doxazosin alone and similar outcomes to finasteride.^[6] CombAT used dutasteride with tamsulosin, required an IPSS of 12 or more, a prostate of 30 mL or more and PSA of 1.5 ng/mL or more, and had no placebo arm; combination therapy was superior to tamsulosin but not significantly to dutasteride for AUR or BPH-related surgery.^[1][2]

Guidelines and approvals

• AUA (Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia, 2026), statement 24. In patients with LUTS/BPH and an estimated prostate volume >30 cc and/or PSA >1.5 ng/mL, clinicians should offer a 5-ARI in combination with an alpha-blocker as a treatment option .^[6]
• EAU (Non-Neurogenic Male LUTS, update March 2026). Offer combination treatment with an alpha-1-blocker and a 5-alpha-reductase inhibitor to men with moderate-to-severe LUTS and an increased risk of disease progression (for example prostate volume >40 mL) .^[9]
• FDA (June 14, 2010). JALYN, the fixed-dose capsule of dutasteride 0.5 mg and tamsulosin 0.4 mg, was approved for symptomatic BPH in men with an enlarged prostate; the label states it is not approved for prostate cancer prevention.^[10][3]

Report history

CombAT report history

Published	Report	Cutoff	Headline results	Citation
2008	2-year symptom endpoint · secondary	—	24-month change in IPSS, combination versus tamsulosin: -6.2 points vs -4.3 points; difference -1.8; CI -2.23–-1.4; P <0.001 Met 24-month change in IPSS, combination versus dutasteride: -6.2 points vs -4.9 points; difference -1.3; CI -1.69–-0.86; P <0.001 Met 24-month change in peak urinary flow: +2.4 mL/s vs +1.9 mL/s vs +0.9 mL/s; — 24-month percent change in prostate volume: -26.9% vs -28.0% vs 0%; —	Roehrborn CG, Siami P, Barkin J, et al. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. *J Urol.* 2008;179(2):616-621. DOI
2010	4-year clinical outcomes · primary	—	4-year AUR or BPH-related surgery, combination versus tamsulosin: 67/1,610 (4.2%) vs 191/1,611 (11.9%); RR 0.34; CI 0.26–0.45; P <0.001 Met 4-year AUR or BPH-related surgery, combination versus dutasteride: 67/1,610 (4.2%) vs 84/1,623 (5.2%); RR 0.8; CI 0.58–1.11; P 0.18 Not met 4-year AUR and BPH-related surgery with the first occurrence of each event counted separately: AUR 36 (2.2%); surgery 38 (2.4%) vs AUR 44 (2.7%); surgery 56 (3.5%) vs AUR 109 (6.8%); surgery 126 (7.8%); — Descriptive 4-year first BPH clinical progression event: 203/1,610 (12.6%) vs 289/1,623 (17.8%) vs 347/1,611 (21.5%); — Met 48-month change in IPSS, combination versus tamsulosin: -6.3 points vs -3.8 points; difference -2.5; CI -2.96–-2.07; P <0.001 Met 48-month change in IPSS, combination versus dutasteride: -6.3 points vs -5.3 points; difference -0.96; CI -1.4–-0.52; P <0.001 Met 48-month change in peak urinary flow: +2.4 mL/s vs +2.0 mL/s vs +0.7 mL/s; — 48-month percent change in prostate volume: -27.3% vs -28.0% vs +4.6%; —	Roehrborn CG, Siami P, Barkin J, et al. 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(1):123-131. DOI
2011-02-18	Baseline subgroups, 4 years · post-hoc	—	Combination versus tamsulosin by baseline subgroup: Post hoc. Combination reduced AUR or BPH-related surgery versus tamsulosin in subgroups with baseline prostate volume above 42 mL, in all PSA subgroups and in all other baseline subgroups (P 0.001 or less). The abstract gives no counts.; — Combination versus tamsulosin and dutasteride by baseline subgroup: Post hoc. Combination reduced the relative risk of clinical progression versus tamsulosin in all baseline subgroups and versus dutasteride in most; men with baseline prostate volume of 40 mL or more and PSA of 1.5 ng/mL or more had the larger reductions versus tamsulosin.; —	Roehrborn CG, Barkin J, Siami P, et al. Clinical outcomes after combined therapy with dutasteride plus tamsulosin or either monotherapy in men with benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year results from the randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) trial. *BJU Int.* 2011;107(6):946-954. DOI
2011-02-23	Storage and voiding subscores, 4 years · secondary	—	4-year adjusted mean difference in IPSS storage subscore, combination versus monotherapy: -0.43 versus dutasteride; -0.96 versus tamsulosin; — 4-year adjusted mean difference in IPSS voiding subscore, combination versus monotherapy: -0.51 versus dutasteride; -1.60 versus tamsulosin; — Combination versus dutasteride by baseline prostate volume: Combination was better than dutasteride in men with baseline prostate volume of 30 to under 58 mL but not at 58 mL or more.; —	Montorsi F, Roehrborn C, Garcia-Penit J, et al. The effects of dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH): 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. *BJU Int.* 2011;107(9):1426-1431. DOI

---

References

1. Roehrborn CG, Siami P, Barkin J, et al. "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(1):123-131. doi:10.1016/j.eururo.2009.09.035

2. GlaxoSmithKline. "Benign Prostatic Hyperplasia Trial With Dutasteride And Tamsulosin Combination Treatment (CombAT)." ClinicalTrials.gov identifier NCT00090103, results posted 2010. clinicaltrials.gov

3. Waylis Therapeutics. JALYN (dutasteride and tamsulosin hydrochloride) capsules, prescribing information. Label effective March 9, 2026. Sections 6.1 and 14. DailyMed

4. Siami P, Roehrborn CG, Barkin J, et al. "Combination Therapy with Dutasteride and Tamsulosin in Men with Moderate-to-Severe Benign Prostatic Hyperplasia and Prostate Enlargement: The CombAT (Combination of Avodart and Tamsulosin) Trial Rationale and Study Design." Contemp Clin Trials. 2007;28(6):770-779. doi:10.1016/j.cct.2007.07.008

5. Roehrborn CG, Siami P, Barkin J, et al. "The Effects of Dutasteride, Tamsulosin and Combination Therapy on Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia and Prostatic Enlargement: 2-Year Results from the CombAT Study." J Urol. 2008;179(2):616-621. doi:10.1016/j.juro.2007.09.084

6. American Urological Association. Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA Guideline. Approved April 2026. Statement 24 and discussion of combination therapy.

7. Roehrborn CG, Barkin J, Siami P, et al. "Clinical Outcomes after Combined Therapy with Dutasteride plus Tamsulosin or Either Monotherapy in Men with Benign Prostatic Hyperplasia (BPH) by Baseline Characteristics: 4-Year Results from the Randomized, Double-Blind Combination of Avodart and Tamsulosin (CombAT) Trial." BJU Int. 2011;107(6):946-954. doi:10.1111/j.1464-410X.2011.10124.x

8. Montorsi F, Roehrborn C, Garcia-Penit J, et al. "The Effects of Dutasteride or Tamsulosin Alone and in Combination on Storage and Voiding Symptoms in Men with Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH): 4-Year Data from the Combination of Avodart and Tamsulosin (CombAT) Study." BJU Int. 2011;107(9):1426-1431. doi:10.1111/j.1464-410X.2011.10129.x

9. Cornu JN, Elterman D, Hashim H, et al. EAU Guidelines on Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS). Arnhem: EAU Guidelines Office; update March 2026. Section 5.2.7.a. uroweb.org

10. U.S. Food and Drug Administration. Drugs@FDA: JALYN (NDA 022460), original approval June 14, 2010. accessdata.fda.gov