ABSTRACT
PURPOSE: Numerous therapeutic options exist in the management
of lower urinarytract symptoms (LUTS)due to benign prostatic
hyperplasia. The efficacy and safety ofBeta-3 agonists (Mirabegron 50
mg) has been sparingly assessed in the published English literature. We
aim to do an efficacy-safety analysis of Mirabegron-Tamsulosin
combination therapy versus tamsulosin-placebo monotherapy in a select
subset of medication virginBPH patients with coexisting predominantly
overactive bladder symptoms (OABS).
METHODS: After prior written informed consent and institutional
ethics clearance, 80 patients of uncomplicated BPH with coexisting OABS
and IPSS of >7 without medical contraindications to the
planned drug therapy were computer randomized and allocated to receive
therapy with either[50mg Mirabegronplus Tamsulosin 0.4 mg
(Intervention arm)]or [Tamsulosin 0.4 mg plus capsule lactobacillus
(Comparator arm)] once daily for a period of 8 weeks. Efficacy was
evaluated usingthe OABS Score (OABSS), mean change in the frequency
ofnocturnal voiding, post void residue (PVR) andinternational prostate
symptom score (IPSS) while safety was assessed by recording treatment
emergent adverse events (TEAE). Follow up visits were done at
2nd, 4th and 8thweeks post therapy and data was analysed using the SPSS vr23(IBM Corp) as per protocol. The protocol was
registered prospectively with the clinical trials registry of India
(CTRI/2018/12/016541).
RESULTS: Patients in both groups were comparable on basis of
their demographic data, preoperative renal function, prostate specific
antigen (PSA), prostate volume and baseline efficacy parameters with the
exception of nocturnal frequency and IPSS storage sub score(IPSS-ss).
Significant improvements were visualised in the primary endpoint total
OABSsubscore (OABSS-ss) at the end of 8 weeks in the combination group
(mean difference -5.62 vs -2.22p< 0.001).Similar significant
improvements were seen with most of the secondary parameters such as the
mean change in voiding episode/night, IPSS, IPSS-ss, OABS-ss, voided
volume/micturition, Qmax, and Quality of Life (QOL) indices
(p<0.001). No significant increase in PVR was observed in the
Mirabegron arm and no patient developed urinary retention. The TEAE were
minor, self-limiting and were managed symptomatically without any
treatment discontinuity.
CONCLUSION: Mirabegron was significantly efficacious and safe
in ameliorating OABS induced by BPH versus placebo. This efficacy can be
safely enhanced by initiating Mirabegron-Tamsulosin combination therapy
from the start in medication virgin patients as opposed to the usual
‘add on therapy’ protocol. This combination appeared to be superior in
terms of overall safety, minimal side effects, better compliance and
tolerability versus Tamsulosin monotherapy particularly in the select
subset of patients of with BPH coexisting/predominant OABS.
KEY WORDS : Mirabegron, Tamsulosin, Benign Prostate
Hyperplasia, Overactive Bladder Symptoms.