RT Journal Article
SR Electronic
T1 Carry-over effects in GAG therapy efficacy trial solution for bladder pain syndrome/interstitial cystitis (GETSBI study): an interim analysis
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e092757
DO 10.1136/bmjopen-2024-092757
VO 15
IS 6
A1 van Ginkel, Charlotte
A1 Groenewoud, J M M
A1 Hoogeboom, Thomas J
A1 Heesakkers, John
A1 Martens, Frank
A1 Janssen, Dick
YR 2025
UL http://bmjopen.bmj.com/content/15/6/e092757.abstract
AB Objectives The double blind, multicentre, randomised, placebo-controlled GAG-therapy Efficacy Trial Solution for Bladder pain syndrome/Interstitial cystitis (GETSBI) study aims to evaluate the efficacy of intravesical glycosaminoglycans therapy with hyaluronic acid and chondroitin sulfate in symptomatic bladder pain syndrome/interstitial cystitis (BPS/IC) patients with Hunner lesions. This trial encompasses multiple methodologies, including a standard randomised controlled trial (RCT), a cross-over trial and an N-of-1 trial. An N-of-1 trial is a multiple crossover trial, usually randomised and often blinded, conducted in a single patient (1). The N-of-1 methodology is, however, only valid under the condition that there is no carry-over effect, meaning a carry-over of effect from an a-priori intervention period into the placebo period. Therefore, it is important to examine any potential carry-over effects to determine the validity of the study protocol concerning the N-of-1 trial part and thereby justifying recruitment.Design Interim analysis for potential carry-over effects.Setting Secondary care, 21 participants.Participants 21 participants, participants concluded part one from the GETSBI study at time of this analysis (October 2023).Outcome measure The primary outcome of the study is the change from baseline in pain intensity, measured by visual analogue scale (VAS) pain. To assess for carry-over effects, the placebo responses on VAS pain were compared between groups with (n=10) and without (n=11) potential carry-over effects. The threshold for a clinically relevant carry-over effect was set at a difference on VAS pain >0.50 points. Data were analysed using descriptive statistics, T-tests, effect sizes and 95% CI. Statistical significance was set at α=0.05.Results The mean baseline VAS pain did not differ (p=0.12) between group A (n=10, VAS 7.52, SD=0.52) and group B (n=11, VAS 6.02, SD=2.47). The mean placebo responses on VAS pain for groups A and B were 0.97 (SD=1.85) and 1.47 (SD=1.81), respectively. The mean carry-over effect was 0.50 (SD=1.83), which was not statistically significant with a 95% CI of −1.17 to 2.17 and p=0.5369.Conclusions This interim analysis shows that an N-of-1 trial probably will be feasible for evaluating non-curative treatment efficacy in chronic disease using only half the patients as are required for a classic RCT. Future analysis will provide a direct comparison of outcomes between the RCT, crossover and the N-of-1 part for a complete evaluation.Trial registration number ClinicalTrials.gov, NCT05518864 (GETSBI study).Data are available upon reasonable request.