Efficacy and Safety of Pregabalin Combined With Educational and Behavioral Intervention for Bladder Pain Syndrome/Interstitial Cystitis

This prospective multicenter parallel randomized controlled trial adopts both intention-to-treat and per-protocol statistical analyses to compare combined pregabalin plus educational-behavioral intervention against behavioral intervention alone for IC/BPS management. Sample size calculation was performed via PASS 11 software. With the presumed 45% response rate of standalone EBMP and an expected 70% response rate in the combined-treatment arm, bilateral α=0.05 and statistical power of 80% were set for calculation. Allowing for a 10% participant dropout rate, the final planned enrollment is 70 subjects per group (140 participants in total).

Random allocation is conducted through the sealedenvelope.com online platform, with allocation concealment realized by sealed opaque envelopes managed by an independent research assistant who is isolated from data collection and direct patient contact. The trial uses an open-label design for both treating clinicians and participants, while outcome assessors remain blinded to group allocation to reduce evaluation bias.

Eligible adults must meet formal AUA and ESSIC IC/BPS diagnostic benchmarks, with urinary symptoms persisting across most days in the latest 3 months and baseline bladder discomfort scores no lower than 3 on the 0-10 Likert scale. Patients satisfying predefined exclusion criteria such as neurogenic bladder dysfunction, severe uncontrolled systemic diseases, pregabalin hypersensitivity, pregnancy and lactation will not be enrolled.

For the combined-treatment arm, pregabalin titration strictly follows the preset dose-escalation protocol. Once intolerable adverse reactions emerge, dosage will be rolled back to the maximum tolerable dose that is maintained until the 12-week endpoint. SPSS 25.0 will be utilized for subsequent statistical analyses. Normal continuous variables will be expressed as mean ± standard deviation, non-normal metrics will be presented with median and interquartile ranges, and appropriate parametric or non-parametric statistical tests as well as chi-square/Fisher's tests will be selected in line with data distribution features, with statistical significance set at P < 0.05. Rigorous source-data monitoring will be implemented across all involved medical centers throughout the whole trial course.

Inclusion criteria

- Adults aged 18 years and older

• Clinically diagnosed with bladder pain syndrome/interstitial cystitis (IC/BPS) in accordance with diagnostic criteria released by AUA and ESSIC, with confounding disorders excluded through clinical workup
• Persistent urinary symptoms across most days in the latest 3 months prior to enrollment
• Participants report bladder pain/discomfort and urinary urgency/frequency scores ≥ 3 on the 0-10 Likert scale over the past 4 weeks

Exclusion criteria

- Symptomatic urethral stricture

• Active neurological diseases that impair bladder or intestinal function
• Active autoimmune disorders or infectious diseases
• History of cystitis secondary to tuberculosis, pelvic radiotherapy or pelvic chemotherapy
• Previous history of non-cutaneous malignant tumors
• Confirmed severe psychiatric disorders at present, including major depressive disorder, bipolar disorder, schizophrenia and other serious mental illnesses
• Severe systemic diseases featuring obvious dysfunction of the heart, lung, liver or kidney
• Confirmed hypersensitivity to pregabalin
• Concomitant use of additional antibiotics or nonsteroidal anti-inflammatory drugs (NSAIDs)
• Pregnancy status
• Lactation period