Table 2 Characteristics of studies included in the systematic review of oral pharmacological and supplementary therapies in BPS/IC
References | Drug | Sample size (n) | Methods | Study duration/follow-up | Intervention | Control | Outcome parameters (primary and secondary) | Results | Adverse event (AE) |
|---|---|---|---|---|---|---|---|---|---|
Sairanen et al. [11] | Cyclosporine A compared to pentosan polysulfate sodium | 64 | Subjects were randomized in a 1:1 ratio to 1.5 mg/kg CyA twice daily or 100 mg PPS three times daily | 6 months | Cyclosporine A (n = 32) | PPS (n = 32) | Daily micturition frequency, mean and maximal voided volume, nocturia episodes, ICSI, ICPI, VAS, subjective GRA | CyA was superior to PPS in all outcome parameters measured at 6 months | More AEs in the CyA group than in the PPS, 29 patients completed the 6-month follow-up in both groups |
Foster et al. [13] | Amitriptyline | 231 | Subjects received an EBMP and were randomized in a 1:1 ratio to either amitriptyline-line or matching placebo | 12 weeks | EBMP + Amitriptyline daily (dose escalation over 6 weeks from 10 to 75 mg per day) (n = 112/13); withdrawn: 23 | EBMP + Placebo (n = 119/136); with-drawn: 17 | GRA, pain, urgency and frequency score (0–10), ICSI, ICPI, 24 h and night-time voiding frequency | Amitriptyline + EBMP improved GRA but not significant statistically, but a minimum 50 mg dose of amitriptyline per day suggested its effectivity compared to placebo (p 0.01) | The side-effect of amitriptyline was acceptable yet adherence to higher doses was low |
Nickel et al. [15] | PD-0299685 | 161 | Subjects were given either 30 mg PD-0299685 daily or 60 mg PD-0299685 daily or placebo | 12 weeks | 30 mg PD-0299685 (n = 40/54); discontinued: 14 60 mg PD-0299685 (n = 31/55); 24 discontinued | Placebo (n = 41/52); discontinued: 11 | NRS, ICSI, MVV, nocturnal frequency, MMF, UEF | PD-0299685 failed to improve pain and other urinary end points | Tolerability was poor, with a dose response for AEs of dizziness, somnolence and nausea |
Matsumoto et al. [20] | Hydrogen-rich water | 28/30 (2 withdrawal) | Subjects were randomized by a 2:1 ratio to receive hydrogen-rich water or placebo water | 8 weeks | Hydrogen-rich water 3 packs/day (n = 18) | Placebo water 3 packs/day (n = 10) | ICSI, ICPI, Parson’s Pelvic Pain, Urgency/Frequency Patient Symptom Scale, VAS score, standard 3-day voiding diary | The overall treatment outcome did not differ significantly between the 2 groups. The VAS scores in 2 patients of hydrogen-rich water group showed valuable improvement | No AEs in all subjects |
Chen et al. [16] | Sildenafil | 48 | Subjects were randomized to daily low-dose sildenafil 25 mg or placebo | 3 months | Daily low-dose sildenafil 25 mg (n = 24) | Placebo (n = 24) | ICSI, ICPI, VAS, micturition diary, PORIS | ICSI and ICPI were significantly improved in treatment group (p < 0.05). Urodynamic index significantly improved at weeks 12 and 3 months after treatment (p < 0.05). No significant change of the VAS between 2 groups except at week 12 | All AEs were mild to moderate and temporary |
Nickel et al. [17] | Pentosan polysulfate sodium (PPS) | 368 | Subjects received PPS 100 mg once (QID), PPS three times (TID) daily, or matching placebo | 24 weeks | PPS 100 mg QID (n = 128) PPS 100 mg TID (n = 122) | Placebo (n = 118) | ICSI, NRS, PORIS, GRA, urgency, frequency | No significant difference between either PPS dose group and placebo or between the PPS dose groups for the primary endpoint | PPS was well tolerated, with similar percentages of discontinued subjects due to an AE (10.2–13.3%) |
Nickel et al. [18] Phase 2 trial | AQX-1125 | 69 | Subjects were randomized to single oral daily capsule of 200 mg AQX-1125 or placebo | 6 weeks | Single daily capsule of 200 mg AQX-1125 (n = 37) | Placebo (n = 32) | NRS, ICSI, ICPI, BPIC-SS, SF-12v2, maximum daily pain and frequency | AQX-1125 significantly improved bladder pain and urinary symptoms at 6 weeks in moderate to severe BPS | AE rates were similar between AQX 1125 (51.4%) and placebo (78.1%). No serious AEs reported |
Murina et al. [12] | Amitriptyline + alpha lipoic acid (ALA) plus omega-3 fatty acids | 84 | Subjects were randomized to amitriptyline or amitriptyline plus ALA 600 mg + n-3 PUFA | 12 weeks | Amitriptyline + preparation containing ALA plus n-3 PUFAs twice daily (n = 43) | Amitriptyline (n = 41) | VAS, McGill-Pain Questionnaire, pelvic floor tonus, dyspareunia | Pain decreased significantly in both groups, with a greater effect seen in the intervention group. There were improvements in dyspareunia and pelvic floor muscle tone in the intervention group | The overall incidence of AEs was low, none led to treatment discontinuation |
Nickel et al. [19] Phase 3 trial | SHIP1 activator | 385 | Subjects were randomized to 100 or 200 mg of an oral SHIP1 activator or placebo once daily | 12 weeks | AQX-1125 100 mg (n = 114) AQX-1125 200 mg (n = 113) | Placebo (n = 114) | NRS, ICSI, BPIC-SS, SF-12v2, maximum daily pain and frequency | No difference in maximum daily bladder pain compared to placebo. No treatment benefit over placebo in the secondary end points of urinary voiding frequency, BPIC-SS, ICSI and GRA | Treatment was well tolerated at both doses |