Endoscopic retrograde cholangiopancreatography (ERCP) is crucial for managing pediatric hepatobiliary diseases but frequently results in postoperative gastrointestinal dysfunction such as delayed flatus and defecation, which can prolong recovery and increase the risk of complications. Nonpharmacological interventions such as acupoint massage and mirabilite application offer potential benefits, but evidence for their efficacy and synergy in children after ERCP is lacking. This study aims to evaluate the individual and combined effects of acupoint massage and abdominal mirabilite application on accelerating gastrointestinal recovery in pediatric patients following ERCP. A single-center, single-blind, randomized controlled trial will be conducted involving 72 children aged between 2 and 12 years who have undergone ERCP. Participants will be randomly allocated to 1 of the 4 groups: acupoint massage group (stimulating ST-36, ST-25, CV-12, and PC-6 for 2 minutes per point; twice daily), mirabilite group (abdominal application for 1 hour; twice daily), combination group (both interventions; at least 1 hour apart), or conventional care group. The primary outcome is the time to first postoperative flatus and defecation. The secondary outcomes include the frequency of postoperative nausea and vomiting and inflammatory markers. Data will be analyzed using intention-to-treat analysis with SPSS, using ANOVA, chi-square, and nonparametric tests as appropriate. This trial is currently in progress, having received funding in January 2023 and July 2023. Participant recruitment commenced on November 1, 2024, with an anticipated completion date of October 30, 2026. As of January 2026, a total of 38 pediatric patients have been enrolled and randomized, while data collection and intervention delivery are ongoing. No interim analysis has been conducted. The final analysis will begin after recruitment and follow-up are complete, with primary results expected to be published in the second half of 2026. This study is the first to rigorously assess the efficacy and potential synergistic effects of acupoint massage and mirabilite application for enhancing gastrointestinal recovery after pediatric ERCP. Positive findings could establish a safe, nonpharmacological protocol to improve postoperative outcomes, reduce hospital stays, and minimize complications in this vulnerable population. International Traditional Medicine Clinical Trial Registry ITMCTR2025000670; https://itmctr.ccebtcm.org.cn/mgt/project/view/3385640124071694411. DERR1-10.2196/87961.

Five-year, prospective, multicenter, real-world study to assess initial delivery, management and long-term effectiveness of a CAD/CAM, 3-D printed oral appliance in the treatment of obstructive sleep apnea: Interim Analysis Update

As with most Sub-Saharan African countries, Nigeria has a rising incidence of cancer, with disproportionate mortality rates. The financial burden of cancer care often results in catastrophic healthcare spending, leading to treatment refusal, disruption, and discontinuation. This is particularly significant in Nigeria, where nearly all patients are uninsured, and out-of-pocket costs often exceed households' ability to pay. Financial navigation programs (FNPs) have been shown to mitigate treatment-related financial toxicity in cancer care and reduce treatment abandonment, but there is a paucity of high-quality data on this intervention in resource-constrained settings. Here, we present a randomized controlled trial to evaluate the impact of a novel FNP in Nigeria. We designed the COST-FIN trial, a multi-site pragmatic single-blinded randomized controlled trial of newly diagnosed (<6weeks from diagnosis) adults (≥18years) with breast, colorectal, or prostate cancer at two tertiary cancer centers in Nigeria. Participants (n = 200) will be randomized (1:1) to either the intervention (FNP) or the control arm and followed for 12months. Data on key individual, treatment, and financial parameters will be collected via structured interviews and chart abstraction at baseline, 3-, 6-, and 12-month follow-up. In addition, participants randomized to the FNP will receive a tailored financial literacy assessment, financial planning support, and enhanced access to resources by trained financial navigators. Primary and secondary outcomes are financial catastrophe (FC) and financial distress (FD), respectively. Exploratory outcomes will include cost-related non-adherence and cost-effectiveness of the program. An interim analysis will be conducted when 50% of the estimated accruals reach 6months of follow-up, with crossover if compelling evidence of benefit is demonstrated at that time point. All participants will be followed for 12months from recruitment. This first-of-its-kind study will provide evidence on the role of FNP in potentially eliminating financial barriers to cancer care in Nigeria. Given the country's renewed interest in cancer control through the passage of the National Cancer Control Plan, findings from this study have the potential to influence policy reform and set the stage for further studies to evaluate the scalability and implementation of similar interventions in resource-limited settings. ClinicalTrials.gov NCT06630962. Registered on Oct 8, 2024.

Some patients report non-specific symptoms after antibiotic therapy for Lyme disease (LD), raising questions about ongoing infection, despite no compelling evidence. We investigated whether xenodiagnosis could detect Borrelia burgdorferi in such patients, and if positive results correlated with symptoms. Participants were adults who completed antibiotic treatment for LD 3-12 months earlier (post-therapy, n=40) or had persistent symptoms for ≥ 12 months after treatment, (post-treatment LD symptoms [PTLDS], n=20). Controls included one patient with erythema migrans (EM), one patient with untreated Lyme arthritis (LA), and 9 healthy volunteers (HV). Participants had 25-30 larval Ixodes scapularis ticks placed; ticks were collected 3-6 days later and tested for B. burgdorferi. The primary analysis evaluated if B. burgdorferi detection by xenodiagnosis was associated with persistence of symptoms in patients during the first year after treatment. This trial is registered with ClinicalTrials.gov, NCT02446626. Recovered ticks included 402 from post-therapy, 314 from PTLDS, 30 from the EM patient, 11 from the LA patient, and 80 from HV. All ticks tested negative for B. burgdorferi except for 1 tick from a recovered patient. An unplanned interim analysis led to the early termination of the study for futility. Xenodiagnosis with larval I. scapularis ticks showed no evidence of B. burgdorferi in most patients after treatment, irrespective of symptoms. This may be due to absence of bacteria or to the low sensitivity of the technique in humans. This method is unlikely to detect persistent B. burgdorferi infection in humans and further research on the use of xenodiagnosis is unwarranted.

Background: Leakage is a major concern for individuals living with a stoma and may negatively impact quality of life (QoL). A digital leakage notification system (DLNS) recently launched in the UK provides timely notifications to users via their smartphone when faeces is detected underneath the baseplate. This provides predictability and enables users to take proactive measures to help avoid leakages outside the baseplate. Methods: A single-arm, observational, longitudinal study of the DLNS, including its associated support service, has been initiated to follow 300 users for a year in the UK to evaluate long-term health benefits of the DLNS and its implications for healthcare resource utilisation in a real-world setting. The DLNS is prescribed by healthcare professionals (HCPs), and all users were invited to participate in the study. Study participants complete questionnaires capturing data on QoL (using the Ostomy Leak Impact tool), number of leakages outside the baseplate, utilisation of ostomy products, interactions with HCPs, and work productivity (using the Work Productivity and Activity Impairment questionnaire) at baseline and then every third month for one year. Data from the planned interim analysis of the first 100 participants who had been in the study for 6 months is presented. Results: Use of the DLNS for 6 months together with the associated support service was associated with a 51% reduction in leakage episodes outside the baseplate (p < 0.001) and great improvements in QoL (p < 0.001). Use of the DLNS reduced the number of unplanned baseplate changes due to worry about leakage by 47% (p < 0.001) and overall was associated with a reduction in the number of baseplates used by 14% (p = 0.002). Total time spent with HCPs related to stoma care was reduced by 65% after 6 months compared with baseline (p < 0.001). Work absenteeism and presenteeism improved significantly with the use of the DLNS. Conclusions: The interim results of this prospective, longitudinal study provided first insights into the long-term benefits of the DLNS in a real-world setting. ClinicalTrials.gov ID: NCT06554015.

Introduction: Retrospective studies and patient surveys investigating cannabis-based products for endometriosis have suggested potential benefits, highlighting the unmet need for effective therapeutic alternatives. This study evaluated the efficacy of cannabidiol in reducing pain among women with surgically treated endometriosis who experienced symptom recurrence. Materials and Methods: This was a single-centre, randomised, parallel, triple-blind, placebo-controlled trial. Eligible participants were women with surgically confirmed endometriosis, previously treated surgically, receiving hormonal therapy, and reporting symptom recurrence. A total of 102 participants were randomized (1:1) into two groups, with 51 allocated to oral cannabidiol-enriched oil (CBDO) and 51 allocated to placebo. The intervention lasted 10 weeks. The oil was administered twice daily with dose escalation from 10 mg/day (week 1) to 150 mg/day (week 9), followed by tapering. The study was terminated after the planned interim analysis due to a lack of difference in the primary outcome and a higher frequency of adverse events in the CBDO group. Primary outcomes were changes in pain intensity (Visual Analogue Scale) and the proportion of participants with ≥30% and ≥50% pain reduction. Participants reported their average perceived pain intensity during the preceding week at each visit. Secondary outcomes included sensory thresholds, psychiatric symptoms, functional impairment, quality of life (QoL), and adverse effects, focusing on common cannabidiol-related symptoms. Results: Approximately 40% of participants in both groups achieved ≥50% pain reduction, and ∼60% reported ≥30% improvement. At the end of treatment, mean pain intensity was 41.6 mm in the CBDO group and 36.8 mm in the placebo group. Although both groups showed significant within-group reductions, differences between groups were not significant. CBDO was associated with improvements in psychological symptoms and several QoL domains but also with more mild adverse events, mainly gastrointestinal symptoms and perceived weight changes. Participants in the placebo group exhibited better scores in physical QoL domains. No serious adverse events occurred. Discussion: Both groups showed consistent and significant pain reduction, but cannabidiol was not superior to placebo. The trial was discontinued at the interim analysis due to the absence of clinically relevant benefit and higher mild adverse-event rates with CBDO. Improvements in placebo-treated participants highlight potential placebo effects and the limited power of secondary analyses.

BackgroundHemodialysis (HD) participants often exhibit significantly lower physical activity (PA) levels than recommended, primarily due to time-intensive dialysis sessions. Physical inactivity in HD participants correlates with increased cardiovascular morbidity and mortality. As cardiovascular disease is the leading cause of death in CKD participants, improving physical activity levels could play a crucial role in cardiovascular risk reduction. Telerehabilitation (TR), combining wearable activity trackers and structured feedback, offers a promising approach to enhance PA in this population. However, evidence regarding its effectiveness in HD participants remains limited.PurposeThis interim analysis evaluates the impact of telerehabilitation on daily step counts in the first 15 participants of an ongoing randomized crossover trial. We hypothesized that TR would significantly increase step counts, contributing to cardiovascular risk reduction, compared to usual care.MethodsThis randomized crossover trial included HD participants (n=15) from Jessa Hospital, Hasselt, Belgium. Participants underwent two 3-month interventions: TR combined with usual care and usual care alone, without a wash-out period. During the TR phase, participants used Fitbit® Charge 5 trackers, receiving weekly structured feedback and step goals aiming for a 10% weekly increase.The presence of a carry-over effect was assessed using an independent t-test comparing cumulative step counts per patient across sequences. No significant carry-over effect was observed (p>0.05). A linear mixed model was fitted with step count as the dependent variable. Fixed effects included sequence, period, and treatment.ResultsThe main daily step count was 3480 steps (SD: 1692). Estimated marginal means suggested higher average daily step counts during TR (4708 steps/day; 95% CI: 3379–6036) compared to standard care (3244 steps/day; 95% CI: 1916–4573). The mean difference between treatments was 1464 steps/day (95% CI: -415.4 to 3342.5), reflecting a moderate effect size(Cohen's d = 0.45). However, the linear mixed model analysis showed that this difference did not reach statistical significance (p=0.12).ConclusionThe interim analysis suggests that telerehabilitation, facilitated by wearable activity trackers and structured feedback, may enhance physical activity in HD participants. Although the mean difference in daily steps between TR and standard care did not reach statistical significance, the moderate effect size suggests a clinically relevant improvement. This potential clinical relevance highlights the promise of TR as an accessible, scalable intervention to improve cardiovascular outcomes in HD participants.Average steps per day

Multi-stage Phase II clinical trials offer advantages over single-stage designs by enabling interim analyses that can accurately inform early termination of the trial if there is evidence that the treatment is likely to be ineffective or effective. However, identifying optimal designs for multi-stage trials poses considerable computational challenges. In addition to having to optimize many integer-valued variables, there are multiple constraints, including order constraints. Traditional exhaustive search methods lack scalability and quickly become computationally infeasible when the number of stages is three or more. To overcome this challenge, we utilize a spherical coordinate system and reformulate the design problem as a continuous optimization task. The new formulation enables us to efficiently use Particle Swarm Optimization (PSO) to extend Simon’s celebrated two-stage Phase II designs to three or more stages. Specifically, we show that our proposed search procedure not only reproduces the two-stage designs and certain three-stage designs found in the literature but also able to achieve the results more efficiently than traditional exhaustive search methods. We provide R codes for reproducing the optimal designs in this paper, which can be easily customized to generate tailor-made optimal designs for specific user needs.

JO40295 (jRCT2080223801) evaluated the efficacy and safety of subcutaneous (SC) mosunetuzumab, in combination with lenalidomide and as monotherapy, in Japanese patients with relapsed/refractory (R/R) follicular lymphoma (FL). We report outcomes from the interim analysis of the FLMOON-2 (≥ 1 prior therapy; mosunetuzumab plus lenalidomide) and primary analysis of the FLMOON-3 (≥ 2 prior therapies; mosunetuzumab monotherapy) cohorts. Mosunetuzumab SC was administered with Cycle (C)1 step-up dosing in both cohorts: C1 Day (D)1, 5mg; C1D8, D15 and C2 onwards, 45mg. In FLMOON-2, oral lenalidomide was administered from C2 onwards, on D1-21 of each cycle. Treatment was administered up to C12 in FLMOON-2 and C8 or C17 in FLMOON-3. The primary endpoint was independent review facility-assessed complete response (CR) rate. At the clinical cut-off date (FLMOON-2: April 4, 2024; FLMOON-3: March 4, 2024), in the efficacy-evaluable populations, CR rate was 92.3% in FLMOON-2 (n = 13) and 100% in FLMOON-3 (n = 5). In the safety-evaluable populations (FLMOON-2, n = 17; FLMOON-3, n = 5), Grade 3/4 adverse events (AEs) occurred in 64.7% of patients in FLMOON-2 and 20.0% in FLMOON-3. No Grade 5 AEs or AEs leading to treatment discontinuation occurred in either cohort. Cytokine release syndrome was reported in 47.1% of patients in FLMOON-2 and 20.0% in FLMOON-3. Serum mosunetuzumab concentration peaked with the third dose of mosunetuzumab in C1 and reached a steady state with repeated dosing. Mosunetuzumab SC, in combination with lenalidomide and as monotherapy, demonstrated promising efficacy with a manageable safety profile in Japanese patients with R/R FL.

BackgroundCytomegalovirus (CMV) establishes lifelong latency and is a risk factor for increased mortality in immunosuppressed individuals. mRNA-1647, an investigational mRNA-based vaccine targeting CMV gB and pentamer antigens, demonstrated acceptable safety and generated antigen-specific humoral and cell-mediated immunogenicity in healthy adults. We present interim analyses of mRNA-1647 safety and immunogenicity from an observer-blind phase 2 trial (NCT05683457) in CMV-seropositive adults ≥18 years with prior allogeneic hematopoietic cell transplantation (HCT).MethodsParticipants were randomized 1:1 to receive a 3-dose primary series of mRNA-1647 150 μg or placebo on Days 42, 67, 92 post-HCT, prior to the critical risk period for CMV reactivation (Day 100 post-HCT and/or CMV prophylaxis cessation). Safety was a primary endpoint. Humoral immunity (secondary endpoint) was measured by cell-based neutralizing antibody (nAb) assays at baseline and 25 days after each dose. CMV-specific T cell responses (gB- and pentamer-specific) were assessed as exploratory endpoints by intracellular cytokine staining and polyfunctionality analyses at baseline and 10 days after each dose. Site personnel remain blinded to safety analyses.ResultsAt data cutoff (7 May 2024), 44 participants were randomized to receive mRNA-1647 or placebo (n=22/group; median age 65 years, 51.2% male, 72.1% White). There were no substantial differences between groups in occurrences of acute or chronic graft-vs-host disease, disease relapse, or serious adverse events. In the mRNA-1647 group vs placebo, nAb GMTs against epithelial cell infection increased ∼2.2-fold after dose 2 and ∼3.2-fold after dose 3. nAb titers against fibroblast infection remained similar between groups. mRNA-1647 induced robust CD4+ and CD8+ T cell responses against CMV-specific glycoproteins (gB, gH, gL) after dose 2, with T cells exhibiting polyfunctionality of substantial magnitude (Figures 1, 2).ConclusionIn high risk seropositive HCT recipients, mRNA-1647 increased nAbs against epithelial cell infection and demonstrated antigen-specific, polyfunctional CD4+ and CD8+ T cell responses. There were no safety concerns on blinded safety assessment. These data support the continued assessment of mRNA-1647 in this population.DisclosuresJessica S. Little, MD, Merck and Company, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support

This study evaluated the effectiveness of Moderna's updated mRNA-1273 vaccine targeting the KP.2 variant, compared to people who did not receive any 2024-2025 COVID-19 vaccine, in preventing COVID-19-associated hospitalizations and medically-attended COVID-19 among adults aged≥18years in the United States during the 2024-2025 season. Data were extracted from linked administrative healthcare claims and electronic health records (EHR) for vaccinations from 23 August 2024 through 23 April 2025 and followed through 30 April 2025. We conducted a retrospective matched cohort study with propensity score weighting to adjust for differences between groups to assess vaccine effectiveness (VE) against COVID-19 outcomes. VE was calculated as 1 minus the hazard ratio (HR) from Cox proportional hazards models. Overall, 596,248 mRNA-1273 KP.2 vaccine recipients were matched 1:1 to unexposed adults. The mean (standard deviation) age was 63 (17) years, with more than half of the population being 65years or older. Approximately 70% of individuals had an underlying medical condition making them high-risk for severe outcomes for COVID-19. VE was 52.8% [95% confidence interval (CI) 34.8%, 65.8%] against COVID-19-related hospitalization and 39.4% (35.0%, 43.5%) against medically-attended COVID-19 over a median follow-up of 55 (interquartile range 32-77) days in an interim analysis. The VE was sustained throughout the entire study period and shown to be 45.2% (37.7%, 51.8%) against COVID-19-related hospitalizations and 33.1% (30.6-35.4%) against medically-attended COVID-19 over a median follow-up of 127 (interquartile range 84-173) days. The mRNA-1273 KP.2 vaccine demonstrated significant incremental effectiveness in preventing hospitalization with COVID-19 and medically-attended COVID-19 in adults during the 2024-2025 season to date. The VE was sustained with longer median follow up time. These findings support ongoing vaccination efforts to mitigate the public health impact of COVID-19.

Proton versus photon radiotherapy for patients with oropharyngeal cancer in the USA: a multicentre, randomised, open-label, non-inferiority phase 3 trial.

BackgroundBlood‐based biomarkers (BBMs) offer a cost‐effective, non‐invasive approach for detecting Alzheimer's disease (AD) pathology, but their impact on improving diagnostic certainty and patient management remains unclear. The PLASMAR study is a prospective, single‐center, blinded, randomized controlled trial assessing the effect of early versus delayed BBM adoption on clinical practice in a public hospital memory clinic. This abstract presents an interim analysis on changes in patient management.MethodFrom February to October 2024, 224 patients with cognitive or behavioral complaints (GDS 2–4) referred to the memory clinic at Hospital del Mar (Barcelona, Spain) were prospectively enrolled. Eligibility criteria are detailed in Table 1. At baseline, blood samples were collected for BBMs, and neurologists assessed diagnostic confidence based on routine clinical evaluation without BBM results. Participants were randomized to the Early (BBM results disclosed at 3 months) or Late (disclosed at 9 months) arms. Patient management changes were compared between arms. Plasma p‐tau217 levels, classified by validated cutoffs, stratified patients into low, intermediate, or high risk for AD pathology.ResultOf 224 enrolled patients, 27 were lost to follow‐up, leaving 197 participants (mean age 71.6 ± 8.9 years; 56.9% female). There were no demographic differences between study arms. Initial diagnoses included SCD (44.7%), MCI (31.4%), or dementia (21.3%), with AD suspected in 30%. By December 2024, 114 patients (87 Early, 27 Late) had BBM results disclosed. AD risk was classified as low (52.4%), intermediate (17.5%), or high (30%). At 3‐months follow‐up, Early‐arm patients had higher discharge rates and initiated AchEIs sooner (p <0.01), while Late‐arm patients more frequently received longitudinal cognitive monitoring (p <0.01). Among SCD patients, Early‐arm participants had higher discharge rates and underwent more lumbar punctures for CSF biomarkers according to their AD pathology risk (p <0.05), while Late‐arm patients were more likely to undergo cognitive monitoring (p <0.001). Among MCI patients, Early‐arm participants had higher discharge rates (p <0.01). Similar trends were observed in the low‐risk AD group (p <0.05).ConclusionThis interim analysis demonstrates that early disclosure of BBM results influences patient management and accelerates the initiation of specific AD treatments, also reducing the need for follow‐up of cognitive assessments.

Phase 2 Prospective Trial of Personalized Radiation Therapy Fractionation in Human Papillomavirus Positive Oropharyngeal Cancer.

FIREFLEYE next 3 years of age efficacy and safety outcomes after intravitreal aflibercept 0.4 mg injection versus laser therapy for retinopathy of prematurity (ROP) in the randomized, FIREFLEYE trial are reported. Children born prematurely (gestational age ≤32 weeks) or with low birth weight (≤1,500 g) were treated for ROP in FIREFLEYE. Efficacy and safety end points for this prespecified interim analysis included ROP status, unfavorable structural outcomes, disease recurrence, treatment of ROP complications, vascularization completion, visual function, adverse events, and growth outcomes. One hundred children were enrolled (aflibercept, 66 [128 eyes]; laser, 34 [64 eyes]). Data for the 3-year analysis were available for 90 children (aflibercept, 60; laser, 30). Most children had no ROP or unfavorable structural outcomes (aflibercept, 98.3% and 93.9% vs. laser, 96.7% and 94.1%), with no ROP reactivation after age 50 weeks. Two children (aflibercept) with re-activated disease received bilateral laser treatment prior to age 50 weeks. Most children could fix and follow a 5-cm toy (aflibercept, 96.6%; laser, 98.3% of eyes). Binocular BCVA (Snellen equivalent) was ≥20/200 and ≥20/40 in 97.8% and 66.7% (aflibercept) versus 100% and 47.8% (laser) of children, respectively. High myopia was present in 8.9% (aflibercept) and 24.1% (laser) of eyes. Adverse events and growth outcomes were as expected for the population. Descriptive analyses of the 3-year outcomes confirm long-term, stable disease control following aflibercept 0.4 mg treatment of severe acute-phase ROP, with age-appropriate visual function, less frequent/severe myopia compared with laser, and no ocular or systemic safety concerns. ClinicalTrials.gov Identifier: NCT04015180.

HighlightsWhat are the main findings?Tumor-Treating Fields (TTFields) therapy was safe and feasible for pediatric diffuse high-grade glioma, the pediatric counterpart of adult glioblastoma.The efficacy of TTFields therapy needs to be assessed in detail after additional patient enrollment in this clinical study.What are the implications of the main findings?Pediatric diffuse high-grade glioma is rare yet highly lethal, underscoring the urgent need for novel therapeutic approaches.This interim analysis supports further clinical development of TTFields therapy to accelerate regulatory approval for pediatric use.Background/Objectives: Although Tumor-Treating Fields (TTFields) therapy is an established treatment modality for adult glioblastoma, clinical data on its efficacy in pediatric brain tumors are extremely scarce. The present study aimed to evaluate the safety of TTFields therapy for pediatric diffuse high-grade glioma (HGG) and to conduct an exploratory analysis of its efficacy. Methods: A prespecified, interim analysis was performed to determine whether the study should be continued on the basis of safety and feasibility data on the first three patients. The target population was children aged 5 to 17 years with newly diagnosed, supratentorial HGG or its first recurrence following frontline therapy. After completion of initial, local treatment for the tumor (surgical removal and/or radiotherapy), all patients received TTFields therapy using OptuneTM for 28 days per course for up to 26 courses until disease progression. Results: The interim analysis, which was completed in October 2022, included three female patients aged 14, 17, and 9 years. All had a histological grade 4 tumor, two of which were radiation-induced, secondary HGG. No serious, treatment-related toxicities or device-related issues were observed. All three patients were able to continue using the device for 75% or more of the time in accordance with the protocol, suggesting that the treatment was feasible. The MRI findings of two patients indicated that the treatment has a potential antitumor effect. Based on these results, the study was resumed and is currently being continued at multiple centers. Conclusions: The initial results of the prespecified, interim analysis demonstrated that TTFields therapy was safe and feasible for children with HGG. This study was funded by the Japan Agency for Medical Research and Development (AMED) and was registered with the Japan Registry of Clinical Trials (jRCTs032200423).

Recurrent acute pancreatitis (RAP) or acute-on-chronic flares in chronic pancreatitis (CP) have limited preventive options beyond addressing the underlying aetiology. Statins, due to their anti-inflammatory properties, have been proposed as a potential prophylactic treatment. We aimed to evaluate whether simvastatin could reduce the recurrence of pancreatitis. At 23 centres, we conducted a triple-blind, randomised, controlled, superiority trial enrolling patients with at least two episodes of RAP or CP flares in the previous 12 months. Participants were randomly assigned to receive simvastatin or placebo for 1 year. The primary endpoint was the recurrence of pancreatitis. The target sample size was 144 patients; however, an interim analysis was planned in the event of slow recruitment. A total of 85 patients (42.1% women) were included in the interim analysis. In the intention-to-treat analysis, no significant differences were observed regarding recurrence: 46.2% simvastatin versus 44.4% placebo; OR 1.07, 95% CI 0.43 to 2.66; p=0.88, or time to recurrence. No statistically significant differences were observed in recurrence in per-protocol analysis (35.5% simvastatin vs 41.9% placebo; OR 0.76, 95% CI 0.27 to 2.12; p=0.60). Development of diabetes mellitus was more frequent in the simvastatin group (4 vs 0 patients; OR not calculable, p=0.04). This trial, evaluating simvastatin versus placebo for the prevention of pancreatitis, did not demonstrate a reduction in recurrence rate, although results might be underpowered due to early termination. The relationship between statins in these patients and new-onset diabetes requires further investigation. NCT04021498.

Interim analysis of the IRMAA study: Concordance between MRI and histopathological analysis of bladder cancer.

Anbenitamab in previously treated HER2-positive gastric cancer (KC-WISE): pre-specified interim analysis of a randomized, phase III clinical trial.

Understanding non-inferiority trials: Lessons from trials comparing thrombectomy with or without intravenous thrombolysis.