Multicentre Randomised Research Articles

Long-term survival of node-positive breast cancer with complete nodal response to neoadjuvant chemotherapy treated with sentinel lymph node biopsy alone: A meta-analysis.

There exist concerns regarding the use of sentinel lymph node (SLN) biopsy alone in node-positive breast cancer patients who have a clinical/radiological complete response in the axilla and are negative on histopathology after neoadjuvant chemotherapy (NACT). We hereby conducted a meta-analysis examining 5-year overall survival (OS) and disease-free survival (DFS) of such patients. PubMed, the Cochrane CENTRAL library, Embase, Web of Science, and Scopus were searched up to 30th July 2024 for studies reporting survival data. OS and DFS were pooled in a meta-analysis. Subgroup analysis was conducted based on the location of the study, pre-NACT node assessment, and SLN mapping technique. Random-effects meta-regression was conducted for the following moderators: age, initial T3-4, initial N2-3, breast-conserving surgery, breast pathological complete response (pCR), number of SLN removed, adjuvant radiotherapy, endocrine therapy, and follow-up Results: 16 studies with 5249 patients were included. Meta-analysis showed that node-positive breast cancer patients showing nodal pCR after NACT and undergoing only SLN biopsy had a 5-year OS and DFS of 94% (95% CI: 92%, 96%) and 89% (95% CI: 87%, 92%) respectively. There was not much variation in the survival rate on sensitivity and subgroup analyses. Meta-regression showed that OS and DFS were higher in studies with a greater number of patients receiving endocrine therapy. Breast cancer patients with cN+ who achieve a complete clinical/radiological axillary response after NACT and subsequently become SLN biopsy negative may have high rates of DFS and OS after 5 years. Given the high degree of heterogeneity, results should be interpreted with caution. We do not recommend change in treatment plans given the high risk of bias and large heterogeneity in the patient population included in the studies. Only high-quality large multicentric randomised trials can provide better evidence.

Bioceramics for Guided Bone Regeneration: A Multicenter Randomized Controlled Trial.

To compare the clinical effectiveness of a novel bioceramic (BC) with a control xenograft (BO) for guided bone regeneration (GBR) performed simultaneously with implant placement. This clinical study enrolled patients with insufficient bone volume who required GBR during implant placement to increase bone width using either BC or BO. Outcome measures included a dimensional reduction in buccal bone thickness measured by cone beam computed tomography performed immediately post-surgery and at 6 months postoperatively (ΔHBBT), soft tissue healing at 14 days, 1 month, and 6 months postoperatively, and complications rates. The primary outcome was the change in buccal bone thickness around the implant. Of the total 152 patients included, 76 from each group received BC and BO treatments. The ΔHBBT in BC and BO groups were -0.276 mm (-0.432, -0.121) and -0.614 mm (-0.769, -0.459) mm, respectively, rejecting the null hypothesis. No significant difference in soft tissue healing was observed between the two groups, with no inflammatory changes in 96.05% and 90.79% of the BC and BO groups, respectively, at 2 weeks postoperatively. However, the BC group exhibited a lower overall complication rate (3.95%), including mild inflammation, poor soft tissue healing, and bone graft extrusion in 3 out of 76 patients. Both BC and BO demonstrated favorable outcomes in bone regeneration and soft tissue healing when used for simultaneous implant placement and bone augmentation.

Brief Mindfulness-Based CognitiveTherapy in Women WithMyocardialInfarction: Results of a Multicenter Randomized Controlled Trial.

Elevated perceived stress is associated with adverse outcomes following myocardial infarction (MI) and may account for poorer recovery among women vs men. This randomized controlled trial tested effects of a mindfulness-based intervention on stress levels among women with MI. Women with elevated stress (Perceived Stress Scale [PSS-4]≥6) at least 2months after MI were enrolled from 12 hospitals in the United States and Canada and via community advertising. Participants were randomized to a remotely delivered mindfulness intervention (MBCT-Brief) or heart disease education, both 8weeks long. Follow-up was 6months. Changes in stress (PSS-10; primary outcome) and secondary outcomes (depressive symptoms, anxiety, quality of life, disease-specific health status, actigraphy-assessed sleep) were compared between groups. The sample included 130 women with MI (mean age 59.8±12.8years, 34% racial/ethnic minorities). In intention-to-treat analysis, PSS-10 scores declined in the MBCT-Brief arm (-0.52 [95% CI: -0.77 to -0.28]) but not the heart disease education arm (-0.19 [95% CI: -0.45 to 0.06]; group×time interaction P=0.070). The effect was stronger in per-protocol analysis of participants who completed≥4 intervention sessions (P=0.049). There were no significant differences in secondary outcomes in intention-to-treat or per-protocol analyses. Within the MBCT-Brief arm, more frequent mindfulness practice was associated with greater reductions in stress (P=0.007), depressive symptoms (P=0.017), and anxiety (P=0.036). MBCT-Brief was associated with greater 6-month reductions in stress than an active control among adherent participants. More frequent mindfulness practice was associated with greater improvements in psychological outcomes. Strategies to engage women with MI in mindfulness training and support regular home practice may enhance these effects.

WCN25-2797 Multicenter Randomized Trial Investigating the Efficacy of the NORA-App in Diabetic Kidney Disease Patients

WCN25-2797 Multicenter Randomized Trial Investigating the Efficacy of the NORA-App in Diabetic Kidney Disease Patients

"Minimal-Advice" on Salt Intake: Results of a Multicentre Pilot Randomised Controlled Trial on Hypertensive Patients.

A strong and well-known association exists between salt consumption, potassium intake, and cardiovascular diseases. MINISAL-SIIA results showed high salt and low potassium consumption in Italian hypertensive patients. In addition, a recent Italian survey showed that the degree of knowledge and behaviour about salt was directly interrelated, suggesting a key role of the educational approach. The present multicentre randomised controlled trial study aimed to evaluate the efficacy of a short-time dietary educational intervention by a physician, only during the first visit, on sodium and potassium intake in hypertensive patients. Two-hundred-thirty hypertensive subjects participating in the MINISAL-SIIA study were enrolled for this study. After the randomisation, the participants were stratified into the educational intervention (EI) group (n = 109) and control group (C) (n = 121). Anthropometric indexes and blood pressure (BP) measurements were taken in the single-centre, and 24-hour urinary sodium (UrNa) and potassium (UrK) excretion were centrally measured. After 3 months, there was a reduction in BP, UrNa, and body weight, and an increase in UrK in EI. By contrast, a lower decrease in BP was found in the C group, and a slight rise in UrNa and no substantial change in UrK were revealed. BP changes were positively and significantly associated with changes in UrNa only in EI. The main results of this trial indicate that a single brief educational intervention by a physician can lead to a reduction in salt intake and BP, and increased potassium consumption in hypertensive patients, without adverse effects. ClinicalTrial.gov registration number: NCT06651437.

The Protocol for the Multi-Ethnic, multi-centre raNdomised controlled trial of a low-energy Diet for improving functional status in heart failure with Preserved ejection fraction (AMEND Preserved)

IntroductionHeart failure with preserved ejection fraction (HFpEF) is characterised by severe exercise intolerance, particularly in those living with obesity. Low-energy meal-replacement plans (MRPs) have shown significant weight loss and potential...

Comparison of the effectiveness of intra-infrapatellar fat pad and intra-articular glucocorticoid injection in knee osteoarthritis patients with Hoffa’s synovitis: protocol for a multicentre randomised controlled trial

IntroductionThe infrapatellar fat pad and synovium are the sites of immune cell infiltration and the origin of proinflammation. Studies have shown that Hoffa’s synovitis may be a sign of early-stage...

Safety and efficacy of high dose buprenorphine initiation in fentanyl positive emergency department patients

Background: The safety and efficacy of high dose buprenorphine (BUP) induction in fentanyl positive emergency department patients (high dose BUP) study includes two clinical trials funded through the helping to end addiction long-termSM initiative. The study tests whether initiation and continuation of BUP at higher doses and over a shorter time period than currently recommended is safe, tolerable and effective. Methods: Trial 1 is a head-to-head comparison of the safety, tolerability and feasibility of high dose BUP initiation (32 mg) and continuation (24 mg) as compared to standard dose BUP initiation (12 mg) and continuation (16 mg). Trial 2 is a small pilot multicenter randomized, double blind clinical trial in 80 participants, randomized 1:1, that will provide preliminary efficacy data. The primary outcome measure for trial 1 is the frequency of dose treatment-emergent adverse events (TEAEs) grade 3 (per common terminology criteria for adverse events v5.0 (CTCAE v5.0)), including but not limited to bradypnea <8, oxygen saturation<88% on room air and/or rescue naloxone administration. The primary outcome measure for trial 2 is the proportion of participants engaged in comprehensive addiction treatment at 7-days post ED initiation. Conclusions: The results of these trials will provide crucial data on the safety, feasibility and efficacy of high-dose ED BUP initiation and continuation in fentanyl positive ED patients and inform incorporation of high-dose BUP initiation into ED care for patients with OUD. Trial registration: ClinicalTrials.gov ID: NCT05589181

Clinical efficacy of Tuina therapy combined with traditional Chinese exercises in the treatment of symptomatic lumbar disc herniation: a multicentre randomised controlled trial protocol

BackgroundLow back pain and lower extremity sensory and functional abnormalities are common symptoms of lumbar disc herniation (LDH), which can easily cause walking dysfunction and significantly impair the quality of life of patients. Tuina and traditional Chinese exercises (TCEs) are effective in relieving pain and restoring dysfunction, and both are often used in China as a combination of passive therapy and active exercise to ease symptoms in patients with LDH. However, the majority of current clinical trials on the treatment of LDH with Tuina or TCEs are single-centre clinical studies, and the quality of these studies is generally low. Furthermore, clear evidence of clinical efficacy as to whether Tuina combined with TCEs is superior to single TCEs for improving dysfunction and pain in patients with LDH is lacking.Methods/designThe design is a multicentre, assessor-blinded clinical randomised controlled trial. A total of 166 patients with LDH (aged 18–65 years) were recruited from four centres and randomly assigned at a 1:1 ratio to two groups: the TCE group and the Tuina combined with the TCE group. Each group received three treatments over the course of 1 week for a total of 4 weeks. The primary outcome indicator was the Oswestry Disability Index, whereas the secondary outcome indicators were the Short Form of Quality of Life Scale, the Short-Form McGill Pain Questionnaire Scale, and gait analysis. Assessments were made before the treatment, at the end of the treatment, and at the third and sixth months’ follow-ups. Gait analysis was only used for comparison between the two groups before and after treatment, and did not involve follow-up. Adverse events occurring during the trial were faithfully recorded.ConclusionThe results of this study are expected to provide a more effective research protocol for symptomatic LDH and an evidence-based rationale for the efficacy and safety of Tuina combined with TCEs in the treatment of symptomatic LDH.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=209956, identifier ChiCTR2300077361.

Treatment for Lateropulsion in Standard Clinical Practice: A Multicenter Randomized Controlled Trial

Background Post-stroke lateropulsion with pusher syndrome (LP) severely impacts postural control and daily activities. In Japan, while a knee-ankle-foot orthosis (KAFO) is recommended for LP treatment, a gait exercise assist robot (GEAR) is also used. Objective We investigated the effectiveness of gait training using a GEAR and KAFO in improving LP. Methods Thirty-six stroke patients with LP were randomly assigned to GEAR or KAFO groups, and received 50-min daily sessions for 2 weeks. Both the GEAR group, using robot assistance, and the KAFO group, with therapist assistance, engaged in gait training with a goal of 30 min per session. Primary outcomes were changes in Burke Lateropulsion Scale (BLS) and Scale for Contraversive Pushing (SCP) scores. Results Seventeen participants in each group completed their respective interventions. Both groups showed marked improvements in BLS and SCP scores (all p < 0.001). Although the GEAR group achieved greater walking distances and step counts ( p < 0.01 each), overall BLS and SCP improvements did not significantly differ between the groups ( p = 0.51 and 0.84, respectively). Both interventions demonstrated comparable LP improvement to previous studies. Conclusions We found no significant difference in the treatment effects between the two interventions, indicating both to be effective.

P0981 Comparative efficacy of standard vs enhanced dose treatment with infliximab in the management of acute severe ulcerative colitis: a single centre retrospective cohort study

Abstract Background Acute severe ulcerative colitis (ASUC) often requires rescue therapy with infliximab, typically administered at an initial dose of 5mg/kg or 10mg/kg. There is some uncertainty regarding the optimal dose of infliximab for rescue therapy and current guidance leaves this to the discretion of the treating clinician. A previous multicentre randomised controlled trial (PREDICT-UC) did not find a significant difference in clinical response or colectomy rates between 5mg/kg and 10mg/kg of infliximab in steroid-refractory ASUC 1. This study aimed to compare the clinical outcomes of patients receiving either 5mg/kg or 10mg/kg infliximab in the management of ASUC. Methods This retrospective cohort study examined patients with ASUC who were treated with rescue infliximab between 2019 and 2022. Patients were categorised into two groups based on the dose received; 5mg/kg and 10mg/kg. Demographic and clinical variables, including age, sex, disease extent (Montreal classification), and prior treatments (no prior treatment, 5-ASA, biologics), were recorded. The outcomes measured included remission (defined as sustained remission at 1 year), the need for surgery, the requirement for additional doses of infliximab, or change in biological agent. Outcomes at 1 month, 6 months, and 1 year were also recorded. Chi-square tests were used to analyse differences between the two treatment groups. Results Of the 50 UC patients, 60% received 5 mg/kg, and 40% received 10 mg/kg. No significant differences were found between the 5 mg/kg and 10 mg/kg infliximab treatment groups for outcomes including surgery (p = 1.00), remission (p = 0.22), and biologic switch (p = 0.22). Additionally, no significant differences were observed when categorising patients by pre-existing treatment (p = 0.06) or disease severity subgroups (E1, E2, E3). When assessing the effect of severe disease markers on treatment outcomes, no significant difference in colectomy rates was found between the two groups for CRP > 50 mg/L (p = 0.34) and albumin < 25 g/L (p = 0.13). Conclusion This study showed no significant difference in the clinical outcomes between patients receiving 5mg/kg and 10mg/kg infliximab for the management of ASUC. These findings suggest that escalating the dose to 10mg/kg does not provide a clear clinical advantage in reducing the need for surgery or achieving sustained remission. Larger, multicentre studies with more diverse patient populations are needed to further investigate the potential benefits of higher infliximab dosing in this clinical context.

A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study).

Options for 'treatment-resistant bipolar depression' (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option. To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD. A multi-centre randomised, double-blind controlled trial including participants ⩾18 years old with TRBD (failure to respond, tolerate or clinical contraindication/patient refusal of ⩾2 of quetiapine, olanzapine, lamotrigine or lurasidone) randomised 1:1 to pramipexole (max 2.5 mg/day salt weight) or placebo added to ongoing mood stabiliser (n = 39). Primary outcome: Quick Inventory of Depressive Symptoms, Self-rated (QIDS-SR) at 12 weeks. Up to 48 weeks follow-up. Pramipexole (n = 18) was associated with a greater reduction in QIDS-SR score at 12 weeks versus placebo (n = 21, 4.4 (4.8) vs 2.1 (5.1)): a medium sized (d = -0.72) but not statistically significant difference (95% CI: -0.4 to 6.3, p = 0.087). Similarly, there was a non-significant approximate 2-point (d = -0.76) improvement in pleasure at 6 weeks (95% CI: -0.11 to 4.20). Significant advantages of pramipexole on QIDS-SR score (6.28 points: 95% CI: 1.85-10.71) and psychosocial function (5.36 points: 95% CI: 0.38-10.35) were seen at 36 weeks post-randomisation, and on the response (46% vs 6%; p = 0.026) and remission (31% vs 0%; p = 0.030) rates at trial exit (48 weeks or last available data after 16 weeks for those affected by the early study closure). Hypomania ratings were significantly higher at 12 weeks. Otherwise, pramipexole was well tolerated. Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and function were observed. Pramipexole use was complicated by dose titration and increased hypomanic symptoms. The small sample size limits interpretation. Furthermore, larger randomised placebo-controlled trials are warranted.

Evaluation of an e-self-management intervention (Happy Hands app) for hand osteoarthritis: Study protocol for a multicentre randomised controlled trial

ObjectiveThis protocol paper describes the rationale and design of a randomised controlled trial (RCT) that aims to evaluate the (cost-)effectiveness of a 12 week e-self-management intervention (Happy Hands app) in people with hand osteoarthritis (HOA).MethodsIn this multicentre RCT, 376 people with HOA will be recruited from all four health regions in Norway. Consenting participants will be randomly allocated to either a control group receiving usual care or an intervention group receiving the Happy Hands app in addition to usual care. Primary outcome will be measured at 3-months follow-up as the proportion of participants classified as OMERACT-OARSI responders (a composite score comprising change in pain, function, and disease activity), analysed using logistic regression. Secondary outcomes, including pain, hand function, stiffness, quality-of-care, health-related quality-of-life, grip strength, adherence and healthcare costs will be measured at 3- and 6-months follow-up.ResultsRecruitment was initiated in November 2022 with a total of 386 participants recruited by August 2023, 194 in the intervention group and 192 in the control group. Data collection was completed in February 2024.DiscussionTo our knowledge, this is one of the first large-scale, multicentre RCTs assessing the (cost-)effectiveness of a self-management program delivered through a smartphone app for people with HOA. The results from this trial can enhance our understanding of the role technology can play in managing HOA.Trial registrationNCT05568875 (https://clinicaltrials.gov/study/NCT05568875, pre-registered October 3, 2022).

Compelling Evidence Regarding Long-Term Performance of Highly Cross-Linked Versus Conventional Polyethylene in TKA at 10 Years: Commentary on an article by Harold I. Salmons, MD, et al.: "Multicenter Randomized Clinical Trial of Highly Cross-Linked Polyethylene Versus Conventional Polyethylene in 518 Primary TKAs at 10 Years".

Compelling Evidence Regarding Long-Term Performance of Highly Cross-Linked Versus Conventional Polyethylene in TKA at 10 Years: Commentary on an article by Harold I. Salmons, MD, et al.: "Multicenter Randomized Clinical Trial of Highly Cross-Linked Polyethylene Versus Conventional Polyethylene in 518 Primary TKAs at 10 Years".

Supported Mindfulness-Based Self-Help Intervention as an Adjunctive Treatment for Rapid Symptom Change in Emotional Disorders: A Practice-Oriented Multicenter Randomized Controlled Trial

Introduction: Rapid symptom relief is crucial for individuals with emotional disorders. The current study aimed to determine whether facilitator-supported mindfulness-based self-help (MBSH) intervention as an adjunctive treatment could provide rapid improvement for individuals with emotional disorders. Methods: A practice-oriented randomized controlled trial was conducted on a sample of 302 patients with emotional disorders from four centers. Participants were randomly assigned to either MBSH+TAU (treatment as usual; n = 152) or TAU-only group (n = 150). Assessments were conducted at baseline, week 3, week 5, immediately after intervention and at a 3-month follow-up. Primary outcomes included self-reported and clinician-reported anxiety and depression symptoms. Secondary outcomes included mindfulness, physical symptoms, perceived stress, sleep quality, and inner peace. Results: The MBSH+TAU group achieved significantly greater improvements in all primary and secondary outcome measures as compared with TAU-only immediately after intervention (Cohen’s d = 0.19–0.51). In addition, relatively greater improvements were observed in self-reported depression, mindfulness, physical symptoms, perceived stress, and inner peace as early as week 3 or 5, which were sustained at the 3-month follow-up (Cohen’s d = 0.20–0.34). Conclusions: Facilitator-supported MBSH offers a scalable and effective adjunctive treatment option for patients with emotional disorders in clinical practice, facilitating rapid improvements.

Therapeutic alliance in a stepped digital psychosocial intervention for breast cancer patients: findings from a multicentre randomised controlled trial.

Action mechanisms of therapeutic alliance in stepped and digital interventions remain unclear. (a) To compare the development of therapeutic alliance between psychosocial treatment as usual (PTAU) and a stepped digital intervention designed to prevent distress in cancer patients; (b) to analyse the level of agreement between patients' and therapists' therapeutic alliance ratings; and (c) to explore variables associated with therapeutic alliance in the digital intervention. A multicentre randomised controlled trial with 184 newly diagnosed breast cancer women was conducted. Patients were assigned to digital intervention or PTAU. Therapeutic alliance was assessed at 3, 6 and 12 months after inclusion using the working alliance inventory for patients and therapists. Age, usability (system usability scale), satisfaction (visual analogue scale), type and amount of patient-therapist communication were analysed as associated variables. Patients and therapists established high therapeutic alliance in the digital intervention, although significantly lower compared with PTAU. The development of patients' therapeutic alliance did not differ between interventions, unlike that of the therapists. No agreement was found between patients' and therapists' therapeutic alliance ratings. Patients' therapeutic alliance was associated with usability and satisfaction with app, whereas therapists' therapeutic alliance was associated with satisfaction with monitoring platform. A stepped digital intervention for cancer patients could develop and maintain strong therapeutic alliance. Neither the type nor amount of communication affected patients' therapeutic alliance, suggesting that flexible and available digital communication fosters a sense of care and connection. The association between usability and satisfaction with digital tools highlights their importance as key therapeutic alliance components in digital settings.

Rationale and design of a multicentre randomised controlled trial on circulating tumour DNA-guided neoadjuvant treatment strategy for locally advanced rectal cancer (CINTS-R)

BackgroundThe traditional neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision has been widely accepted as the standard treatment for patients with locally advanced rectal cancer (LARC). New strategies such as...

Improving the accUracy of Referrals to the emerGency departmEnt of patieNts with chesT pain using the modified HEART score in Emergency Medical Transport (URGENT 2.0): protocol for a multicentre randomised controlled trial

IntroductionIschaemic heart disease is the single most common cause of death worldwide. Traditionally, distinguishing patients with cardiac ischaemia from patients with less alarming disease, in prehospital triage of chest pain,...

A Tailored Electronic Survivorship Care Plan for Prostate Cancer Survivors: A Multicenter Randomized Controlled Trial.

Although the provision of a survivorship care plan (SCP) has been recommended after prostate cancer (PCa) treatment, there have been no randomized controlled trials to examine their impact. The objective of this study was to evaluate the effect of a tailored PCa-SCP intervention provided to early-stage PCa survivors. A prospective, parallel 1:1 randomized controlled trial was conducted at 3 sites across Canada. Early-stage PCa survivors were randomized (n = 189; 64% response rate) to receive PCa-SCP intervention or usual care. Assessments were performed at baseline, 6 months, and 12 months. The primary outcome was change in patient activation (Patient Activation Measure-13); secondary outcomes included satisfaction with information, self-management support, prostate-specific quality of life, cancer worry, health care utilization, and health behaviors. For the primary patient activation analyses, no significant group-by-time differences were detected. There were significant between-group differences in (1) satisfaction with information from baseline to 6 months (mean [95% CI]: 7.13 [5.53-8.71]; effect size [ES], 0.34; P < .001) and baseline to 12 months (4.91 [3.06, 7.06], ES, 0.19, P < .001); (2) social integration and support from baseline to 6 months (mean [95% CI]: 0.16 [0.06-0.26]; ES, 0.25; P = .002); and (3) skill and technique acquisition from baseline to 6 months (mean [95% CI]: 0.12 [-0.02 to 0.24]; ES, 0.33; P = .05). No other group-by-time differences were detected. The PCa-SCP intervention did not have a significant effect on patient activation but did increase satisfaction with information and some aspects of self-management support. Although the benefits of the provision of a SCP alone remain unclear, the PCa-SCP intervention is likely a valuable tool that can be built upon as part of a comprehensive approach to enhance the quality of care for PCa survivors. NCT03017456.

Smartphone application-based pulmonary rehabilitation in COPD: a multicentre randomised controlled trial

BackgroundPulmonary rehabilitation (PR) is an essential element of chronic obstructive pulmonary disease (COPD) management. However, access to conventional face-to-face PR programmes is limited.MethodsThis multicentre, randomised controlled trial recruited patients with...