Multicentre Randomised Research Articles

Retraction: Multicenter Randomized Controlled Trial Assessing the Impact of a Cervical Traction Maneuver (Amr's Maneuver) on the Incidence of Postpartum Hemorrhage.

Retraction: A. Hamdy, O. Azmy, R. Lotfy, A. A. Attia, M. M. Elsherbini, A. Al Sawaf, M. M. Soliman, M. F. Sharaf, A. Kamel, M. N. A. El-Raouf, S. Salem, M. A. Rasheed, H. Torky, and E. R. Issak, "Multicenter Randomized Controlled Trial Assessing the Impact of a Cervical Traction Maneuver (Amr's Maneuver) on the Incidence of Postpartum Hemorrhage," International Journal of Gynecology & Obstetrics 144, no. 1 (2019): 56-61. https://doi.org/10.1002/ijgo.12687. A third party raised concerns regarding miscalculated data and discrepancies between the reported sample size and the sample size included in the clinical trial registry. The authors responded to an inquiry by the journal and publisher, and have stated that the prospectively-registered sample size for the trial had changed from 4866 to 804 following the trial start, due to an interim analysis by the IRB and DSMB. Neither this change nor the reason for it were reported in the article. Therefore, the authors' stated original sample size and calculations do not correspond to the number presented in the published article. In addition, an independent review of the available dataset found that the results of all three categorical variables in Table1 are not reproducible and the authors' argument of averaging the two-sided and one-sided Fisher's exact p values is not methodologically sound. The retraction has been agreed to because neither the data nor the results presented in the article can be considered reliable. Author M. M. Soliman disagrees with the retraction. All other authors did not respond to our notice regarding the retraction.

Ten-Year Outcome of a Randomized Trial: Cytoreduction and HIPEC with Mitomycin C Versus Oxaliplatin for Appendiceal Neoplasm with Peritoneal Dissemination.

Appendiceal cancer is a rare disease that has proven difficult to study in prospectively. Our initial reportof this trial showed minor hematologic toxicity with both mitomycin C and oxaliplatin and similar 3-year survival. We now report an update of the first prospective randomized trial for appendiceal cancer with 10-year follow up. Patients with mucinous appendiceal neoplasms and evidence of peritoneal dissemination were enrolled in the Multicenter Randomized Trial to evaluating HIPEC for 120min with oxaliplatin (200mg/M2) or mitomycin C (40mg). Overall survival and disease-free survival were calculated at 10 years and compared between the groups. A total of 121 patients were included in the study. The patients were 57% female, with a mean age of 55.3 years (range 22-82 years). The disease was low grade in 71% and high grade in 29%. The average peritoneal cancer index (PCI) score was 18 (SD 10) in the mitomycin C group and 17.9 (SD 9.4) in the oxaliplatin group (p = 0.94). The 10-year survival rate was 56.2% (SE 7.2) with mitomycin C and 47.5% (SE 8.4) with oxaliplatin, p = 0.83. The 10-year progression-free survival rate in the mitomycin C group was 45.2% (SE 8.4) compared with 50.4% (SE 6.7) in the oxaliplatin group, p = 0.95. Median survival was 9.1 years after HIPEC with oxaliplatin, and median not reached for the mitomycin C group (> 5.6years). Oxaliplatin and mitomycin C have similar long-term efficacy for hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal neoplasms and peritoneal dissemination. Long-term survival is experienced by most patients after cytoreduction surgery (CRS) and HIPEC for appendiceal neoplasms.

A New Centralized Statistical Monitoring Method for Detecting Atypical Distribution of Qualitative Variables in Multicenter Randomized Controlled Trials

Centralized statistical monitoring (CSM) detects clinical trial centers in which the distribution of a variable is atypical compared to its distribution in other centers. Most proposed CSM methods concern quantitative variables. Here we propose a new hierarchical Bayesian beta-binomial (HBBB) method for categorical variables and report the results of a simulation study assessing the performance of the method and of an application study using a real database to assess its usefulness. In the simulation study, sensitivity exceeded 90% when the sample size in the atypical center (N a ) was ≥ 20 and the difference in the proportion of events between the atypical center and the other centers ( δ ) was ≥ 0.4; when N a was ≥ 40 and δ ≥ 0.3; and when N a was ≥ 150 and δ ≥ 0.2. Specificity exceeded 90% when N a was ≥ 150 in all scenarios, and remained between 75% and 90% when N a was lower. In the application study, the method detected two centers in which N a was 50 and 200, and δ was 0.12 and 0.04, respectively. The performance of the HBBB method was similar to that proposed by competing approach. The modeling is easy and specificity is good in many scenarios with a limited sample size.

A Nutritional Strategy Based on Multiple Components for Glycemic Control in Type 2 Diabetes: A Multicenter Randomized Controlled Clinical Trial

Background/Objectives: The optimal dietary approach for managing glycemic and metabolic control in type 2 diabetes (T2D) is still uncertain, though it should be tailored for clinical settings. Therefore, we sought to assess the impact of a multicomponent nutritional strategy on glycemic control in T2D patients within a public health system. Methods: NUGLIC was an open-label, parallel-group, superiority, multicenter randomized controlled trial. Participants aged 30 and older with poorly controlled T2D were randomly assigned to either (1) a personalized dietary prescription (control group, n = 185) or (2) a strategy involving targeted nutritional advising, mindfulness techniques, and short message services (NUGLIC [intervention] group, n = 186). The primary outcomes were glycated hemoglobin (HbA1c, %) measured after 24 weeks and glycemic control, defined as having an HbA1c > 7% at baseline and achieving ≤7% after follow-up, or having HbA1c ≤ 7% at baseline and reducing the use of glucose-lowering medications post-follow-up. The secondary outcomes included cardiometabolic features, self-care practices, diet quality, and quality of life. Results: A total of 371 participants were included in an intention-to-treat analysis for the primary outcomes. At six months, both groups exhibited a reduction in HbA1c levels compared to the baseline (NUGLIC group: −0.6% [95% confidence interval (CI) −0.9; −0.3], p < 0.001; control group: −0.5% [95% CI −0.7; −0.3], p < 0.001). However, no significant differences were observed between the groups in terms of HbA1c after follow-up (intervention group: 8.1%; control group: 8.3%; difference: −0.2% [95% CI −0.5; 0.1], p = 0.30) or glycemic control (NUGLIC group: 19.9%; control group: 18.9%; odds ratio 0.96 [95% CI 0.56; 1.67], p = 0.89). While the control group showed an improvement in overall diet quality, no significant differences emerged between the groups by the end of this study (p = 0.13). There were also no significant differences in other secondary outcomes nor in the use of glucose-lowering medications and adverse events after follow-up. Conclusions: The multicomponent nutritional strategy did not demonstrate superiority over personalized dietary prescriptions in achieving glycemic control for participants with poorly managed T2D. In this sense, both nutritional interventions could be used in clinical practice to improve HbA1c levels, considering the profile and preferences of individuals.

Effect of high-flow nasal therapy on patient-centred outcomes in patients at high risk of postoperative pulmonary complications after cardiac surgery: update to the statistical analysis plan for NOTACS, a multicentre adaptive randomised controlled trial

BackgroundThe NOTACS trial will assess the efficacy, safety and cost-effectiveness of high-flow nasal therapy (HFNT) compared to standard oxygen therapy (SOT) on the outcomes of patients after cardiac surgery.Methods/designNOTACS is an adaptive, international, multicentre, parallel group, randomised controlled trial, with a pre-planned interim sample size re-estimation (SSR). A minimum of 850 patients will be randomised 1:1 to receive either HFNT or SOT. The primary outcome is days alive and at home in the first 90 days after the planned surgery (DAH90), with a number of secondary analyses and cost-effectiveness analyses also planned. The interim SSR will take place after a minimum of 300 patients have been followed up for 90 days and will allow for the sample size to increase up to a maximum of 1280 patients.ResultsThis manuscript provides detailed descriptions of the design of the NOTACS trial and the analyses to be undertaken at the interim and final analyses. The main purpose of the interim analysis is to assess safety and to perform a sample size re-estimation. The main purpose of the final analysis is to examine the safety, efficacy and cost-effectiveness of HFNT compared to SOT on the outcomes of patients after cardiac surgery.DiscussionThis manuscript outlines the key features of the NOTACS statistical analysis plan and was submitted to the journal before the final analysis in order to preserve scientific integrity under an adaptive design framework. A previous version of this SAP was published prior to the interim analysis (Dawson, 2022). The NOTACS SAP closely follows published guidelines for the content of SAPs in clinical trials (Gamble, 2017).Trial registrationISRCTN14092678. (13 May 2020).

Evaluation of Internal and External Hexagon Connections in Immediately Loaded Full-Arch Rehabilitations: A Multicenter Randomized Split-Mouth Controlled Trial With a 6-Year Follow-Up.

Full-arch immediate loading rehabilitations are now a widely used rehabilitation method that guarantees predictable medium- and long-term results. Numerous factors can influence its success and stability in the medium and long term. Among these the implant-abutment connection seems to play an important role, however there is still little information on which is the most suitable in this type of treatment. The aim of the present multicenter split-mouth controlled trial is to evaluate whether external hexagonal connections (EHC) and internal hexagonal connections (IHC) can influence success, bone resorption and peri-implant parameters in immediate-load full-arch rehabilitations. Twenty patients were rehabilitated with immediately loaded fixed full-arch rehabilitations. All the implants presented the same macro- and micro-topography but different implant-abutment connection. IHC were used in one randomly selected side of the jaw and EHC was used in the other side. Outcome measures were implant survival rate, peri-implant marginal bone loss (MBL), plaque index (PI), probing depth (PD), and bleeding on probing (BoP) evaluated at 3, 6, 12, 36, and 72-month post-loading. Technical and biological complications were recorded. In 20 patients, 43 EHC and 40 IHC implants were placed. Between 32 and 72 months of follow-up two patients withdrew (died) and no implants were lost. The cumulative survival rate (CSR) was 97.44% for EHC implants and 97.22% for IHC implants. The MBL presented a resorption of 2 mm in the EHC group and 1.9 mm in the IHC group. No statistically significant differences were found between the two groups for any of the parameters at any time. No biological or technical complications were detected between the 36th and 72nd month of follow-up. After 72 months in function, both internal and external hexagon connections provided good clinical outcomes and were not associated with any significant difference in the clinical outcomes.

Multicenter Randomized Clinical Trial of Highly Cross-Linked Polyethylene Versus Conventional Polyethylene in 518 Primary TKAs at 10 Years

Background: Second-generation highly cross-linked polyethylene (HXLPE) has revolutionized total hip arthroplasty. However, the long-term risks and benefits of HXLPE in primary total knee arthroplasty (TKA) remain unknown. This randomized clinical trial evaluated implant survivorship, complications, radiographic results, and clinical outcomes of HXLPE and conventional ultra-high molecular weight polyethylene (UHMWPE) inserts in primary TKAs. Methods: We enrolled 518 patients (518 knees) who underwent primary TKA in 3 centers within 1 tertiary referral network. The mean age was 67 years, the mean body mass index was 32 kg/m2, and 58% of the patients were women. All of the patients underwent primary TKA with a cemented posterior-stabilized tibial insert and patellar resurfacing. Randomization proceeded via stratified dynamic allocation. The patients were blinded to their study group allocation: those in the control group (254 knees) underwent TKA with an UHMWPE insert (N2Vac; Stryker); those in the treatment group (264 knees) received an HXLPE insert (X3; Stryker). Kaplan-Meier survivorship, radiographic results, and clinical outcomes were assessed. This trial was registered with ClinicalTrials.gov. The mean follow-up was 11 years. Results: The 10-year overall survivorship free from any revision and from any reoperation was 96% and 94%, respectively. There were no differences in the risk of revision or reoperation between the groups (p > 0.05). There were a total of 19 revisions. Revision indications included periprosthetic joint infection (14 knees), instability (4 knees), and open reduction and internal fixation (ORIF) for a patellar fracture due to osteolysis around a UHMWPE insert (1 knee). There were no revisions due to polyethylene wear, osteolysis, or fracture of the post in the HXLPE group. The radiographic results and clinical outcomes were otherwise similar. Conclusions: Notably, no wear-related failures were identified in the HXLPE group, but there was 1 case of osteolysis in the UHMWPE group. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Comparison of group versus individual patient education for promoting safety skills of patients with autoimmune rheumatic diseases treated with biologics: a multicentre randomised controlled trial.

To evaluate the effectiveness of a nurse-led intervention combining face-to-face and group education sessions for the acquisition of safety skills by patients with autoimmune rheumatic diseases treated with biologics. This multicentre randomised controlled trial compared two individual patient education sessions against a combination of an individual session at baseline and a group session 3months later. The primary outcome was a validated questionnaire (BioSecure) scored at 6 and 12 months that assessed competencies and problem-solving abilities to deal with fever, infection, vaccination, and daily situations. Secondary outcomes were fear of disease, anxiety, depression, and arthritis helplessness. A total of 120 patients with rheumatoid arthritis and spondyloarthritis were included (60 in each arm) from 7 French rheumatology departments; 99 patients completed the study at 6months and 83 at 12months. The BioSecure score improved at 6months in both arms (delta from baseline 14.9 ± 16.3 in face-to-face education and 16.0 ± 17.9 in combined education) and was maintained for 12months but no significant difference was found between arms at 6 and 12months (p = 0.35 and p = 0.13, respectively). Fear of disease, arthritis helplessness, and anxiety were improved at 6 and 12months with no difference between arms. Educating patients using individual nurse-led sessions or a combination of individual and group sessions increased their safety skills on biologics, with no superiority shown for the combined format. Given the time and resources required to educate patients, these results could lead to potential cost savings. Clinical Trials: NCT03838939. Key Points • Face-to-face patient education has been shown effective in promoting safety skills of patients treated with biologics compared to information provided by the rheumatologist in usual care. • This randomised controlled trial showed that a patient education format combining one individual and one group session was not superior to two individual sessions regarding safety skills assessed at 6 and 12months • Safety skills, fear of disease, arthritis helplessness, and anxiety were improved in both arms. • As the most common barriers to the implementation of patient education are constraints in time and resources, these results could lead to potential cost savings.

Comment on “Long-Term Outcome of Immediate Versus Postponed Intervention in Patients With Infected Necrotizing Pancreatitis (POINTER)”: Multicenter Randomized Trial

Comment on “Long-Term Outcome of Immediate Versus Postponed Intervention in Patients With Infected Necrotizing Pancreatitis (POINTER)”: Multicenter Randomized Trial

Study Protocol for a French Multicenter Randomized Controlled Trial Evaluating the Medico-Economic Impact of Surgical versus Endovascular Arteriovenous Access Creation for Hemodialysis in End-Stage Renal Disease (ENDO-FAV)

IntroductionVascular access is indispensable for performing hemodialysis in patients with end-stage renal disease. The Kidney Disease Outcome Quality Initiative and the French Health Authority advocate for native arteriovenous fistulas (AVFs) as a primary option due to their association with lower morbidity, mortality, and enhanced quality of life. However, a significant proportion of AVFs fail to mature, and many require multiple re-interventions, increasing overall costs.To address these issues, endovascular techniques for AVF creation have been developed. These methods use energy-based technologies, avoiding vessel dissection and preserving perivascular tissues. Initial results are promising but these devices are expensive, and the technical act of creating an endovenous fistula is not recorded in the coding of the common classification of medical procedures (CCAM) and, as such, cannot be reimbursed by health insurance in France. While international studies suggest their effectiveness, no French studies have yet replicated or confirmed these findings in the local context, which would help support a reimbursement request from health insurance. MethodsThis protocol represents the first French medico-economic study to compare the two available endovascular AVF creation devices (Ellipsys® and WaveLinQ®) with traditional open surgery. This multicentre, comparative clinical trial will randomize patients into two parallel groups: (1) endovascular AVF creation using either the WaveLinQ® or Ellipsys® device, and (2) surgical proximal AVF creation (brachio-cephalic/basilic). Randomization will be balanced and stratified by centre and dialysis timing. Follow-up assessments will occur at 1 week, 1, 3, 6, 12, and 18 months. The primary objective is to evaluate the cost-effectiveness of endovascular AVF creation compared to open surgery from the perspective of the French healthcare system. The primary endpoint is the cost-utility ratio (cost per QALY gained) of endovascular AVF versus open surgery. Utility is assessed using the EQ-5D-5L questionnaire, with costs derived from micro-costing and the National Health Data System (SNDS). Secondary outcomes include health economics with total costs at 18 and 36 months, success rate of vascular access creation, AVF maturation and functionality, recirculation rates, early and late access failures, cannulation success, primary and secondary patency, reintervention rates, and adverse events. Based on a cost-utility threshold of €30,000 per QALY, cost difference estimates, and standard deviations from previous studies, anticipated sample size is 126 patients per group (endovascular and surgical), totaling 252 patients with about 142 patients for the Ellipsys® device and 110 patients for WaveLinQ®, based on the capacity of 7 centers using Ellipsys® and 4 centers using WaveLinQ®. ConclusionsThis multicentric randomized controlled trial will provide contemporary data on clinical outcomes and prognoses for endovascular AVF techniques, potentially establishing endovascular methods as a viable and cost-effective alternative to traditional surgical AVF creation.

Nurse‐Led Screening‐Triggered Early Specialized Palliative Care Program for Patients With Advanced Lung Cancer: A Multicenter Randomized Controlled Trial

ABSTRACTBackgroundWe aimed to examine the effectiveness of a nurse‐led, screening‐triggered early specialized palliative care intervention program for patients with advanced lung cancer.MethodsPatients with advanced lung cancer who underwent initial chemotherapy were randomized to intervention and usual care groups between January 2017 and September 2019. The intervention comprised comprehensive needs assessments, counseling, and service coordination by advanced‐level nurses. Patients in the usual care group received the usual oncological care. The primary end point was a change in the trial outcome index (TOI) scores from baseline to 12 weeks. The secondary end‐points were TOI scores at week 20, depression, anxiety, and survival.ResultsIn total, 102 patients were assigned to each group. Compared with the usual care group, no significant improvement in TOI scores was observed at 12 weeks in the intervention group (mean group difference: 2.13; 90% confidence interval: −0.70, 4.95; p = 0.107, one‐sided), whereas significant improvement was observed at 20 weeks (3.58; 90% confidence interval: 0.15, 7.00; p = 0.043). There were no significant differences in the change from baseline depression and anxiety between the groups from baseline at week 12 and 20 weeks (depression: p = 0.60 and 0.10, anxiety: p = 0.78 and 0.067). Survival did not significantly differ between the groups (median survival time: 12.1 vs. 11.1 months; p = 0.302).ConclusionsNurse‐led, screening‐triggered, early specialized palliative care did not show significant superiority over usual care during the 12‐week study period. However, it may have yielded delayed clinical benefits, such as improved quality of life and this feasible model can be acceptable in clinical practice.Trial Registration: The University Hospital Medical Information Network Clinical Trials Registry: UMIN000025491

Paclitaxel- or sirolimus-coated balloons used for ArterioVEnous fistulas-2 (PAVE-2): study protocol for a randomised controlled trial to determine the efficacy of paclitaxel- or sirolimus-coated balloons in arteriovenous fistulas used for haemodialysis

BackgroundIn view of the conflicting results from previous studies, the benefit of paclitaxel-coated balloons for arteriovenous fistulas is uncertain and equipoise remains. Although an industry-led trial testing the efficacy of sirolimus-coated balloons in AVFs is in progress, the benefit of sirolimus-coated balloons for arteriovenous fistulas is currently unknown. The purpose of this trial is to compare the efficacy of additional paclitaxel-coated or sirolimus-coated balloons on outcomes after a plain balloon fistuloplasty to preserve the patency of arteriovenous fistulae used for haemodialysis.MethodsThe study design is a multicentre randomised controlled trial. Following a successful plain balloon fistuloplasty, participants will be randomised to further treatment with a paclitaxel-coated balloon, a sirolimus-coated balloon, or an uncoated control balloon. We will recruit 642 patients, each with one or two treatment segments, over a 3-year period. Patients will remain in the trial and be followed up for 1 year. The primary endpoint is time to loss of treatment segment primary patency. Cox-proportional hazards models will be used to estimate hazard ratios for the time to loss of treatment segment primary patency for each treatment group relative to the control group. Analysis of the primary endpoint will be based on treatment segments rather than participants and a shared frailty will be estimated to account for the clustering of treatment segments within patients. Secondary endpoints are time to loss of primary patency at any treatment segment; time to end of access circuit primary patency; time to AVF abandonment; number of radiological or surgical interventions; adverse events; intima-media thickness and degree of stenosis at 3 months on ultrasound; and patient quality of life assessed by EQ-5D-5L and VASQoL.DiscussionThe three-armed design in this proposal will provide an answer on the efficacy of both paclitaxel- and sirolimus-coated balloons in the same trial. This trial is likely to provide a clear answer regarding the efficacy of drug-coated balloons for arteriovenous fistulas.Trial registrationISRCTN ISRCTN40182296. Registered on 4 August 2023.

A meta-analysis of randomised controlled trials comparing optical coherence tomography-guided against angiography-guided revascularisation

Abstract Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) offers more in-depth assessment of plaque morphology, vessel sizing and post-PCI stent deployment characteristics than angiography guidance alone. Previous studies have demonstrated superiority of OCT-guided compared to angiography-guided PCI in stent implantation and expansion, with no difference in safety outcomes. Despite this, adoption of OCT-guided PCI remains low in clinical practice due to its increased procedural time, larger contrast volume, and added cost. Two large multicentre international randomised controlled trials (RCTs) were recently published. We therefore aimed to perform an up-to-date meta-analysis of RCTs comparing OCT-guided revascularisation against angiography-guided revascularisation on hard clinical outcomes. A comprehensive search of PubMed/MEDLINE and Ovid/Embase was performed, of which only RCTs were included. Two authors identified relevant articles and extracted the data independently. Any disagreements were resolved by a third author. Clinical outcome data was extracted from each study and then pooled to determine the overall risk ratio (RR) and confidence interval (CI) collectively. This was calculated with random-effects model using the Mantel-Haenszel method. All reported P values are two-sided, with significance set at P<0.05. A total of ten RCTs involving a total of 5062 patients were included. After an average follow-up of 20 months, there was no significant difference in the trial-defined composite endpoint between OCT-guided versus angiography guided revascularisation [6.8% versus 7.9%, RR 0.85, 95% CI (0.69 to 1.03), P=0.10, heterogeneity (I2)=0%]. There was also no significant difference in cardiac death [1.0% versus 1.6%, RR 0.61, 95% CI (0.36 to 1.02), P=0.06, heterogeneity (I2)=0%, Figure 1a], myocardial infarction [3.2% versus 3.7%, RR 0.86, 95% CI (0.65 to 1.15), P=0.31, I2=0%, Figure 1b] and target lesion or vessel repeat revascularisation [3.8% versus 4.1%, RR 0.95, 95% CI (0.72 to 1.25), P=0.70, I2=0%, Figure 1c] between the two arms. However, the OCT-guided revascularisation arm was associated with a significantly lower rate of stent thrombosis [0.8% versus 1.5%, RR 0.57, 95% CI (0.33 to 0.97), P=0.04, I2=0%, Figure 1d] than the angiography-guided revascularisation arm. The number-needed-to-treat (NNT) by OCT-guided revascularisation to reduce one additional stent thrombosis event was 143. In conclusion, our findings show the use of OCT-guided revascularisation led to a significant reduction in stent thrombosis compared to angiography-guided revascularisation, but there was no difference in cardiac death, myocardial infarction and repeat revascularisation. The NNT for stent thrombosis was 143 patients. Further research is needed to identity those subgroups most likely to benefit from OCT-guided revascularisation before it can be more widely adopted to significantly impact on clinical care.

HD grid versus circular mapping catheter for assessment of pulmonary vein (pv) reconnections

Abstract Background Traditionally, circular mapping catheters (CMC) have been considered superior to other designs for mapping pulmonary vein reconnections due to the circular shape of the PV ostium. The grid multipolar catheter produces higher definition maps potentially overcoming the disadvantage of being rectangular. Purpose We assessed the acute procedural results, comparing Grid versus CMC in the setting of PV re-isolation to understand if one was superior to the other. Methods In this multicentre randomised controlled trial, 169 patients (62% male; median age 66 years [22-83) underwent repeat ablation, between July 2021 and March 2023, for recurrent symptomatic atrial arrhythmias. We undertook two LA maps for patients, utilising the Grid and the CMC. Blinded maps were collected with both catheters, followed by randomisation to one map for analysis and ablation. The primary outcome was the radiofrequency time required to isolate the pulmonary veins. Secondary outcomes include LA mapping time and density for both catheters, ability to identify pulmonary vein sleeves and duration of the ablation procedure. Results 126 patients had PV reconnections. 66 patients (64% male; median age 65 years [22-83]) in the Grid arm and 60 patients (68% male; median age 65.5 years [31-83]) in the CMC arm. There was one pericardial effusion and one TIA. There was no significant difference (p=0.202) found in the RF time required to achieve PV isolation in both Grid (mean RF time 200 ± 232 secs) vs CMC (mean RF time 169 ± 298 secs) arms. There was no significant difference (p=0.407) found between LA mapping time for the CMC (mean 1047 ± 454 seconds) and the Grid (Median 1080 ± 440 seconds). There was no significant difference (p=0.411) found in the total procedure time for the CMC (mean 122.7 minutes) and the HD grid (130 minutes). There were significantly more (p<0.001) PV mapping points identified with the grid (mean 354±213 points) than the CMC (mean 234±154 points) arm. There was no significant difference in PV sleeve reconnections found (p=0.106) between the grid (120 PV sleeve reconnections with a mean 1.4±0.71 reconnections) and the CMC (98 PV sleeve reconnections with a mean 1.52±0.72 reconnections). Both maps were analysed to assess reconnections on opposing catheter arms. The grid identified 20 PV sleeve reconnections not visible on the CMC, whilst 9 were visible on the CMC and not the grid. Conclusion There was no significant difference found in RF time, mapping time and overall procedure time. The Grid identified more reconnections not seen with the CMC and had an overall improved mapping density suggesting that this configuration could be superior for LA mapping.

An international multicentre randomised controlled trial of en bloc resection of bladder tumour vs conventional transurethral resection of bladder tumour: first results of the en bloc resection of urothelium carcinoma of the bladder (EBRUC) II trial.

To determine the safety and oncological advantages of en bloc resection of bladder tumour (ERBT) vs conventional transurethral resection of bladder tumour (cTURBT) in terms of resection quality, staging quality, and safety. We conducted a single-blinded randomised controlled trial at seven European hospitals with the following inclusion criteria: first diagnosis of non-muscle-invasive bladder cancer, no singular carcinoma in situ, and tumour size >4.3 mm. Patients were randomised intraoperatively in a 1:1 ratio to either the ERBT or cTURBT group. Outcome analysis was performed using the chi-square test, t-test, and multivariate regression analysis. A total of 97 patients were randomised into the study (cTURBT = 40, ERBT = 57). A switch to cTURBT was necessary in two patients (3.5%) and 11.5% of the screened patients were preoperatively excluded for ERBT. There was no difference in the specimen presence of detrusor muscle with 73.7% in cTURBT and 67.3% in ERBT specimens (P = 0.69). There were no significant differences in mean operative time (ERBT 27.6 vs cTURBT 25.4 min, P = 0.450) or mean resection time (ERBT 16.3 vs cTURBT 15.5 min, P = 0.732). Overall the complication rate did not differ significantly (ERBT 18.2% vs cTURBT 7.5%, P = 0.142). Bladder perforations occurred significantly more often in the ERBT group (ERBT seven vs cTURBT none, P = 0.020). R0 status was reported more often after ERBT, whilst a second resection was significantly less frequent after ERBT (P = 0.018). Recurrence rates were comparable for both techniques after 6 months of follow-up. The feasibility of ERBT is higher than previously reported. Whereas other perioperative and safety parameters are comparable to cTURBT, bladder perforations occurred significantly more often in the ERBT group and raised safety concerns. This is why this trial was terminated.

Thursday, July 11, 202410:30 AM - 11:30 AMPPP01 Presentation Time: 10:30 AM: Late Toxicity of Intermediate / High Risk Prostate Cancer Patients Treated within a Multicenter Randomized Trial Comparing External Beam Radiotherapy Alone with External Beam Radiotherapy Plus a Brachytherapy Boost

Thursday, July 11, 202410:30 AM - 11:30 AMPPP01 Presentation Time: 10:30 AM: Late Toxicity of Intermediate / High Risk Prostate Cancer Patients Treated within a Multicenter Randomized Trial Comparing External Beam Radiotherapy Alone with External Beam Radiotherapy Plus a Brachytherapy Boost

Treat-to-target fixed dose rituximab retreatment versus fixed interval retreatment with disease activity-guided rituximab dose optimisation for patients with rheumatoid arthritis: study protocol for a multicentre randomised controlled superiority trial focusing on long-term disease impact (RITUXERA)

BackgroundThe optimal retreatment strategy with rituximab for rheumatoid arthritis (RA) remains a point of discussion. Depending on local guidelines, rituximab can either be administered at fixed intervals or when losing disease control, balancing therapeutic effectiveness with drug overexposure. However, treatment based on loss of disease control may significantly affect patients’ lives, provoking uncertainty and potentially leading to progressive joint damage. Moreover, as low-dose rituximab proved to be effective in treating RA while decreasing toxicity, drug exposure may be limited by tapering down rituximab doses guided by disease activity.MethodsRITUXERA is a 104-week open-label multicentre randomised controlled superiority trial. In total, 134 patients with RA treated with rituximab will be 1:1 randomised when in need of retreatment (DAS28-CRP ≥ 3.2 with previous rituximab administration at least 24 weeks earlier) to either a treat-to-target-driven fixed dose retreatment strategy (usual care group) or fixed interval disease-activity guided dose optimisation strategy (experimental group). The usual care group will be retreated with fixed rituximab doses (1 × 1000 mg IV) in case of loss of disease control (DAS28-CRP ≥ 3.2). The experimental group will receive a 24-weekly rituximab treatment while tapering down the dose in a decreasing sequence if DAS28-CRP ≤ 3.2: 1 × 1000 mg IV (maximal dose), 1 × 500 mg IV, and 1 × 200 mg IV (minimal dose). If DAS28-CRP exceeds 3.2 at the six-monthly retreatment, patients will receive and remain on the previous effective dose. Study visits are planned every 12 weeks. Primary outcome is the comparison of longitudinal patient-reported disease impact over 104 weeks, measured with the Rheumatoid Arthritis Impact of Disease (RAID) instrument, analysed using a linear mixed model. Main secondary outcome is the comparison of longitudinal disease activity (DAS28-CRP) over 104 weeks.DiscussionThe RITUXERA trial aims to explore the optimal retreatment strategy with rituximab for RA in terms of long-term patient-reported disease impact, by proposing a fixed interval disease activity-guided dose optimisation strategy as compared to a treat-to-target fixed dose strategy.Trial registrationCTIS 2023–506638-59–01 (registration date: 07 September 2023), ClinicalTrials.gov NCT06003283 (registration date: 17 August 2023).

Urgent Contrast-Enhanced Computed Tomography before Early Colonoscopy in the Management of Colonic Diverticular Bleeding: A Multicenter Randomized Controlled Trial

Introduction: Contrast-enhanced computed tomography (CE-CT) has been gaining attention as an initial investigation in the management of colonic diverticular bleeding (CDB), yet the role of CE-CT other than its diagnostic yield has not been adequately clarified. We aimed to determine whether the use of urgent CE-CT improves identification of stigmata of recent hemorrhage (SRH) in subsequently performed early colonoscopy (≤24 h of arrival) or other clinical outcomes of CDB. Methods: We conducted a randomized, open-label, controlled trial at 23 institutions in Japan. Outpatients with suspected CDB were randomly assigned to undergo either urgent CE-CT followed by early colonoscopy (urgent-CE-CT + early-colonoscopy group) or early colonoscopy alone (early-colonoscopy group). The primary outcome was SRH identification. Secondary outcomes included successful endoscopic hemostasis, early (<30 days) and late (<1 year) rebleeding, length of hospital stay, and transfusion requirements. Results: In total, 240 patients, mostly in a hemodynamically stable condition, were randomized. A contrast extravasation on CE-CT was observed in 20 of 115 patients (17.4%) in the urgent-CE-CT + early-colonoscopy group. SRH was identified in 23 of 115 patients (20.0%) in the urgent-CE-CT + early-colonoscopy group and 21 of 118 patients (17.8%) in the early-colonoscopy group (difference, 2.2; 95% confidence interval [CI], −7.9 to 12.3; p = 0.739). Successful endoscopic hemostasis was achieved in 21 patients in each group (18.3% and 17.8%, respectively) (difference, 0.5; 95% CI, −9.4 to 10.4; p = 1.000). There were also no significant differences between groups in early and late rebleeding, length of hospital stay, and transfusion requirements. Conclusion: The use of urgent CE-CT before early colonoscopy did not improve SRH identification or other clinical outcomes in patients with suspected CDB in a hemodynamically stable condition. The routine use of urgent CE-CT as an initial investigation is not recommended in this population, also considering the low rate of extravasation-positive cases (UMIN registry number, UMIN000026865).

A Suicide Attempt Multicomponent Intervention Treatment (SAMIT Program): study protocol for a multicentric randomised controlled trial.

Suicide has become a first-order public health concern, especially following the negative impact of COVID-19 on the mental health of the general population. Few studies have analysed the effects of early psychotherapeutic interventions on subjects who have attempted suicide, and even fewer have focused on those hospitalized in non-psychiatric units after a Medically Serious Suicide Attempt (MSSA). The main aim of this study is to describe the protocol designed to evaluate the effectiveness of individual psychological treatment for patients hospitalized after an MSSA. The secondary objectives of the study are: (1) to evaluate the impact on quality of life and other psychosocial variables of patients with a recent MSSA who receive early psychological intervention; (2) to analyse the biological, psychological, and clinical impact of early psychotherapeutic treatment on subjects hospitalized after an MSSA. A longitudinal randomised controlled trial will be conducted with patients over 16 years of age admitted to two general hospitals. The case intervention group will enrol for 8-sessions of individual psychotherapy, Suicide Attempts Multi-component Intervention Treatment (SAMIT), combining Dialectical Behaviour Therapy (DBT), Mentalization-Based Therapy (MBT), and Narrative approaches, while the control group will receive a treatment-as-usual intervention (TAU). Longitudinal assessment will be conducted at baseline (before treatment), post-treatment, and 3, 6, and 12 months after. The main outcome variable will be re-attempting suicide during follow-up. Some psychotherapeutic interventions, usually implemented in outpatient, have proven to be effective in preventing suicidal behaviours. The combination of some of these may be a powerful treatment for preventing future SA in patients hospitalised after an MSSA, which is the most severely suicidal subgroup. Moreover, assessment of the biological, clinical and psychometric impact of this new intervention on patients during the first year after the attempt may help understand some of the multi-level factors associated with the effectiveness of psychotherapeutic interventions in MSSAs. The prevalence of high suicide rates requires the design of effective psychological interventions for their prevention, and also in order to design new pharmacological and psychological treatments. ClinicalTrials.gov ID: NCT06238414. Date of registration: 1st February 2024, final update is protocol version 3.0, 19th March 2024.

Use of the Win Ratio for Analysis of Stroke Trials: Description, Illustration, and Planned Use in the Second European Carotid Surgery Trial (ECST-2).

Randomized trials in stroke often focus on outcomes beyond a single clinical event. Trials of stroke prevention commonly use composite outcomes that include multiple components (eg, death, stroke, or myocardial infarction). A major limitation is that all events count equally but may differ markedly in terms of clinical severity. Trials in acute stroke often use ordinal outcomes or scale scores. Limitations include the requirement for statistical assumptions and the difficulty of handling the competing risk of death. We introduce the win ratio as an alternative method. It works by placing components of a composite into a hierarchy, whereby clinically more important outcomes take priority over less important ones. We illustrate how it works using data from 2 major stroke trials: the ICSS (International Carotid Stenting Study, a trial in stroke prevention) and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Potential benefits of the win ratio approach include the possibility to (1) emphasize the clinically most important outcomes, (2) combine components of different outcome types into a composite (eg, a mixture of time-to-event, continuous, and categorical), and (3) naturally handle the competing risk of death in analyses of quantitative outcomes. The win ratio will be used in the upcoming analysis of the ECST-2 (Second European Carotid Surgery Trial), which has a hierarchical primary outcome of (1) time to perioperative death, fatal stroke, or fatal myocardial infarction (most important); (2) time to nonfatal stroke; (3) time to nonfatal myocardial infarction (excluding silent infarcts); and (4) new silent cerebral infarct on brain imaging (least important). The win ratio provides a useful clinically relevant method for analyzing trial outcomes. It has some advantages over conventional methods, and we recommend its wider application in future stroke trials.