Trials最新文献

Background: Although the number of frozen-thawed blastocysts transfer is increasing worldwide, the live birth rate following blastocyst transfer using assisted reproductive technology remains at 30-60%. Thus, improving the pregnancy rate per transfer is an urgent issue. In a previous retrospective study, we evaluated the use of granulocyte-macrophage colony-stimulating factor (GM-CSF)-containing medium for recovery culture to improve the outcomes of frozen-thawed blastocyst transfers. The results demonstrated that the live birth rates increased by approximately 10% following recovery culture in the GM-CSF-containing culture medium. This study aims to prospectively evaluate whether GM-CSF-containing blastocyst recovery culture following thawing increases live birth.

Methods: This is a multicenter, randomized, parallel-group, active-controlled, single-blind trial. The recruitment target is 750 participants meeting the criteria. Enrolled patients are randomized 1:1 to the GM-CSF-containing culture medium group (test group) or the non-GM-CSF-containing culture medium group (control group). The blastocyst recovery culture after warming was defined as an intervention in this study; frozen-thawed blastocysts will be cultured for 3-7 h in GM-CSF-containing medium (test group) or medium without GM-CSF (control group) followed by blastocyst transfer. The primary outcome will be live birth. We will also evaluate embryo transfer outcomes as secondary efficacy endpoints and evaluate perinatal and neonatal outcomes as a safety endpoint.

Discussion: This is the first large-scale prospective study to investigate the efficacy of a GM-CSF-containing medium for frozen-thawed blastocyst transfer. The study findings will provide evidence regarding the efficiency of GM-CSF-containing medium for blastocyst recovery culture after warming.

Trial registration: Japan Registry of Clinical Trials jRCT1040240159. Registered on January 6, 2025.

Background: Intra-hospital transport of critically ill, mechanically ventilated patients is associated with significant physiological risks. Adaptive Minute Ventilation (AMV) is a closed-loop ventilation mode that automatically maintains target minute ventilation. While AMV has shown promise in intensive care unit settings, its performance during intrahospital transport has not yet been evaluated. This trial aims to assess the safety and efficacy of AMV compared with conventional ventilation strategies during patient transport.

Methods: This is a single-centre, open-label, randomized controlled non-inferiority trial conducted at Peking Union Medical College Hospital. Fifty adult patients receiving invasive mechanical ventilation and requiring transport will be randomly assigned (1:1) to either AMV or their pre-transport ventilation mode. The primary endpoint is the change in arterial carbon dioxide pressure (PaCO₂) from 30 min before to 10 min after transport. Secondary outcomes include changes in oxygenation index (PaO₂/FiO₂), peak airway pressure, dynamic compliance, and rapid shallow breathing index. Randomization will be performed using permuted block randomization. Both intention-to-treat and per-protocol analyses will be conducted. Missing data will be handled using multiple imputation. The study protocol has been reviewed and approved by the Ethics Committee of Peking Union Medical College Hospital (Approval No. I-25PJ0781). It was registered in the Chinese Clinical Trial Registry (ChiCTR2500109659) on 23 September 2025 as a retrospective registration.

Discussion: This trial will be the first randomized study to evaluate AMV during intrahospital transport of critically ill patients. The findings will address an important evidence gap in transport ventilation strategies, potentially informing clinical practice on whether AMV provides a safe and effective alternative to conventional modes. By employing a non-inferiority design and standardized transport protocols, the study seeks to generate robust and clinically relevant evidence despite its single-centre setting and relatively small sample size.

Trial registration: Approved by the Ethics Committee of Peking Union Medical College Hospital (Approval No. I-25PJ0781).

Trial registration: ChiCTR, ChiCTR2500109659. Registered 23 September 2025, https://www.chictr.org.cn/hvshowproject.html?id=284847.

Background: As clinical trials increasingly adopt decentralised elements to potentially reduce burden and enhance participant inclusion, data on participant experience and satisfaction becomes essential to inform future decentralised trial designs. This study investigated participant satisfaction in three trial arms: a fully decentralised arm, a hybrid arm and a conventional arm in individuals with type 2 diabetes mellitus.

Methods: RADIAL, a three-arm, low-intervention, phase IV proof-of-concept trial, was set up in six European countries and aimed to evaluate the scientific and operational quality as well as the feasibility of trial approaches with different levels of decentralisation. Participant satisfaction was measured at three time points: at start (week 0), during (week 12), and at the end of the trial (week 24), using digital questionnaires.

Results: In all arms, 72% to 100% of participants were satisfied with overall trial participation, but satisfaction decreased over time in the hybrid arm compared to the conventional arm. Participants reported issues with trial technologies as reasons for their dissatisfaction in the hybrid arm, which was further substantiated by dissatisfaction with specific digital trial components. Satisfaction with the time commitments and data collection was also lower in the hybrid arm than in the conventional arm. Nevertheless, participants in both arms were very satisfied with the comprehensibility of the information before trial start, feeling of safety, interaction with trial staff, and timing of trial appointments, ranging from 92% to 100%. Due to the small number of seven participants in the remote arm, no meaningful conclusions on satisfaction could be drawn in this arm.

Conclusions: Decentralisation seems to be acceptable to trial participants, as trial activities can be responsibly shifted from the research site to participants' homes, e.g. decentralised, without materially impacting participant satisfaction. However, technological issues negatively affected satisfaction in the hybrid arm, highlighting the need to utilise fit-for-purpose technologies and adequately address potential digital challenges in trials. Including participant satisfaction measures in trials deepens the understanding of how participants experience different (decentralised) trial activities, which can help to tailor future trials to their needs.

Trial registration: ClinicalTrials.gov NCT05780151 (2023-03-08) and CTIS 2022-500,449-26-00 (2022-03-28).

Clinical trials involving sexual minority adolescents and young men in low- and middle-income countries have historically been limited due to a combination of structural, social, and scientific barriers that often hinder their participation. In addition, researchers lack the cultural competence or knowledge of inclusive recruitment strategies to effectively engage these populations. In this commentary, we describe the experiences, challenges, and opportunities in establishing youth advisory boards as a pathway to entry into the community, overcoming exclusion, building trust, and incorporating the voices of under-served sexual minority adolescents and young men in clinical trials and the development of community-informed interventions.Trial registration: ClinicalTrials.gov NCT06350682. Registered on February 10, 2026.

Background: Obtaining informed consent can be challenging in emergency and critical care research due to the acute and severe nature of the patient's condition. However, such research is urgently needed to inform practice and optimise patient outcomes. While alternative consent approaches have been commonly used, opinions may vary, particularly among diverse and underserved patient groups and in the context of the recent COVID-19 pandemic. The objective of this review was to assess views of alternative consent methods in emergency and critical care research.

Methods: We conducted a rapid systematic review to understand diverse opinions of alternative consent models used in emergency and critical care research with searches of MEDLINE, EMBASE, PsycINFO, Web of Science and CENTRAL carried out to July 31, 2024. We included quantitative and qualitative studies and summarised findings using narrative synthesis. We specifically investigated underserved groups and consent in the pandemic setting.

Results: From 9974 citations, we screened 289 full-text articles, and included 145 eligible studies from 26 countries. Consent methods included prospective informed consent, deferred consent, surrogate decision maker consent, healthcare professional consent and waived consent. Groups represented included previous trial participants, relatives of trial participants, patients, members of the general public, healthcare providers, researchers, site staff, and research ethics committees. It was recognised that prospective informed consent from the patient is not possible in all scenarios. In general, alternative consent models were acceptable, with emphasis on the inclusion of the patient and relatives in the decision-making process whenever possible. Acceptability of alternative consent models was influenced by previous research participation, experience of critical or emergency illness, perceived risk of participation, and invasiveness of the intervention. Study staff highlighted potential limitations of some alternative consent models, such as unavailability of relatives. Pandemic studies showed an increased need for alternative consent methods, and greater preparedness and engagement with ethics committees to facilitate implementation. Sub-analysis evaluating the views of underserved groups did not show consensus, and accommodations were largely not reported.

Conclusion: Alternative consent models used for emergency, critical care and pandemic research including deferred consent, relative/surrogate decision maker consent, and physician consent were generally acceptable.

Trial registration: PROSPERO CRD42023408305 (April 19, 2023).

Background: Mental disorders can impact parenting negatively, thus placing their children at risk of adversity. The current service support for parents in adult mental health (AMHS) service is limited. The objective of this randomized clinical trial will be to evaluate the effects of a transdiagnostic mentalization-based parenting program (Lighthouse MBT Parenting Program) versus care as usual (CAU) for parents with mental disorders in AMHS in Denmark.

Methods: This trial is designed as an investigator-initiated single-center open-label randomized clinical superiority trial of the Lighthouse MBT Parenting Program compared to CAU for parents with mental disorders. Participants will be recruited from Danish outpatient mental health clinics by the local service providers and will be included if they have a child 0-17 years of age, whom they are in regular contact with. We plan to randomize 170 parents with a 1:1 allocation ratio stratified by parental gender and baseline parenting stress score. The primary outcome will be level of parenting stress (Parenting Stress Index version 4 - Short Form). Secondary outcomes will be child psychological problems and functioning (Strength and Difficulties Questionnaire - Extended version), parental quality of life (brief abbreviated version of the World Health Organization Questionnaire of Life), family functioning (McMaster Family Assessment Device - General Functioning), exposure to child adversity in offspring (Adverse Child Experiences Questionnaire), parenting competence (Parenting Sense of Competence), parental psychiatric symptom severity (Brief Symptom Inventory), parental health-related quality of life and functioning (European Quality of Life - 5 Dimensions - 3 Levels), and parental use of drugs and alcohol (Alcohol Use Disorders Identification Test and the Drug Use Disorders Identification Test - Extended). The primary and secondary outcomes will be assessed before randomization and at 6, 12, and 24 months after randomization. The primary time-point of assessment will be 6 months after randomization for all randomized participants. Exploratory outcomes include key theoretical concepts, including parental mentalizing (Parental Reflective Functioning Questionnaire), mind-mindedness (representational Mind-Mindedness), and epistemic trust (Epistemic Trust, Mistrust, and Credulity Questionnaire). Exploratory outcomes will be assessed at baseline and at 6 months follow-up. Adverse events will be systematically monitored throughout the trial period using the e-journal system.

Discussion: This trial will provide evidence of the effects of a transdiagnostic mentalization-based parenting intervention (Lighthouse MBT Parenting Program) compared to care as usual for parents with mental disorders in adult mental health services in Denmark.

Trial registration: ClinicalTrials.gov: NCT06315114. Registration on 01-03-2024.

Background: Zygomatic implant (ZI) is an effective method for restoring masticatory function and mid-facial appearance in patients with severe alveolar ridge resorption, avoiding complex bone augmentation. Dynamic navigation-assisted surgery has been introduced to improve ZI placement accuracy, with registration being a crucial step. However, the current registration method using fiducial screws is limited by their concentrated placement in the mouth, reducing accuracy around the zygomatic bone. This study aims to evaluate the accuracy and clinical outcomes of a novel minimally invasive registration plate in ZI surgery, guiding its clinical application in dynamic navigation-assisted ZI surgery.

Methods: This is a prospective, single-center, parallel-group, non-inferiority randomized controlled trial conducted at Shanghai Ninth People's Hospital, Shanghai, China. We plan to recruit 20 patients who need ZI restoration. The inclusion criteria include severe atrophy of the maxillary alveolar ridge or maxillary bone defects. The anterior region must have adequate bone volume to allow placement of two temporary implants or at least four pins for registration plate fixation, or existing implants or residual teeth can provide stable fixation for the registration plate. Participants will be randomly assigned in a 1:1 allocation ratio into two groups: control group: dynamic navigation registration using traditional titanium screws; experimental group: dynamic navigation registration using the novel registration plate. The group assignment will be blinded for accuracy evaluators. Entry and exit point and angular deviations of the ZI, surgical time, registration accuracy, patient satisfaction, implant survival rate, and adverse event incidence will be assessed.

Discussion: A novel minimally invasive registration plate has been designed to extend the coverage of registration points to the zygomatic bone, thereby expanding the registration range for dynamic navigation-assisted zygomatic implant placement. This study aims to compare the new registration approach with the conventional titanium screw-based method to evaluate whether it enhances the accuracy of dynamic navigation-assisted zygomatic implant surgery.

Trial registration: Name of the registry: Chinese Clinical Trial Registry (ChiCTR).

Trial registration number: ChiCTR2500103641 (retrospectively registered). Date of registration: 2025-06-03. First planned enrollment: 2024-11-17. URL of trial registry record: https://www.chictr.org.cn/showproj.html?proj=272887.

Background: Postoperative delirium (POD) is common after hip-fracture surgery in older adults and is associated with prolonged hospitalization, increased mortality, and long-term cognitive decline. Previous literature has indicated that dexmedetomidine may reduce delirium when given intra-operatively; however, the benefit of a single nocturnal infusion before surgery has not been evaluated. We hypothesize that pre-operative night-time dexmedetomidine improves sleep quality and attenuates neuro-inflammation, thereby decreasing POD incidence.

Methods: This multicentre, randomized, double-blind, placebo-controlled trial will enroll 560 patients aged 65-90 years undergoing hip-fracture surgery. Participants will be randomly assigned (1:1) to receive an overnight infusion of dexmedetomidine 0.2 µg/kg·h or matching saline from 20:00 to 06:00 a.m. before surgery. The primary endpoint is the incidence of POD during the first 72 h, assessed every 6 h with the 3-Minute Diagnostic Confusion Assessment Method and the relative risk (95% CI) will be calculated using the chi-square test. Secondary outcomes include delirium severity and duration, pain scores, sleep quality, cognitive function at 30 and 180 days, and plasma biomarkers.

Discussion: This protocol evaluates whether the night-before infusion of dexmedetomidine prevents POD in older adults undergoing hip-fracture surgery. If effective, the intervention could easily be implemented in routine peri-operative care.

Trial registration: Chinese Clinical Trial Registry ChiCTR2400087107. Registered on 19 July 2024.

Background: EMBRACE and Retro EMBRACE studies have shown that excellent local control and pelvic control could be achieved with concurrent chemoradiation and MRI-based brachytherapy in carcinoma cervix. Para-aortic nodal failure rates are higher in pelvic node-positive cases as compared to pelvic node-negative cases as demonstrated in EMBRACE studies. The current study aims to find out the benefit of adding prophylactic para-aortic node irradiation in patients of carcinoma cervix who have involved pelvic nodes on volumetric imaging.

Methods: This will be a two-arm, parallel group, phase II/III open-label multicenter randomized controlled trial. Patients will be enrolled in a phase II trial where the primary endpoint will be demonstration of reduction in the risk of para-aortic recurrence. If the primary endpoint is met, a phase III trial will be initiated using the same trial design and intervention. Patients in arm A (control arm) will receive pelvic radiotherapy covering the common iliac nodes with Intensity Modulated Radiotherapy (IMRT) to a dose of 45 Gy/25 fractions over 5 weeks. Radiologically involved lymph nodes will be boosted to a dose of 55 Gy/25 fractions with simultaneous integrated boost (SIB). Patients in arm B (Experimental arm) will receive pelvic and elective para-aortic radiotherapy up to the lower border of the renal vein (IMRT) to dose of 45 Gy/25 fractions over 5 weeks. Radiologically involved lymph nodes will be boosted to a dose of 55 Gy/25 fractions with simultaneous integrated boost (SIB). Concurrent chemotherapy with cisplatin 40 mg/m² weekly will be given during external beam radiotherapy in both the arms. After completion of concurrent chemoradiation, high dose rate (HDR) intracavitary or intracavitary + interstitial brachytherapy will be performed in both the arms.

Discussion: This trial will demonstrate the efficacy of prophylactic para-aortic radiation in pelvic node-positive carcinoma cervix. It also gives an opportunity to standardize and assess the quality-assurance radiotherapy practices in carcinoma cervix across multiple premier institutes of the nation at the same time.

Trial registration: Clinical Trial Registry of India (CTRI): CTRI/2023/08/057075. Registered on 30th August 2023.

Background: Win statistics offer an alternative approach to clinical trials that use survival analysis to analyze composite endpoints. Our objective was to re-analyze data from previously published registry-based randomized controlled trials that produced hazard ratios using win statistics to evaluate the correspondence between them. Good correspondence was defined as both results being positive, negative, or neutral. Win statistics were calculated for these trials to encourage transparency, scientific rigor, and possibly validate results.

Methods: The win ratio ordered events hierarchically by clinical importance for each trial, with all-cause death regarded as most severe, followed by acute myocardial infarction. Further components, i.e., other endpoints, were added subsequently to the hierarchy. Each patient in the treatment group was compared with each patient in the control arm in hierarchical order. The total number of wins for each category in the treatment group was added and divided by the total number of wins in the control group. Win odds were calculated as an extension, which incorporate ties into the calculation.

Results: The results using win statistics showed good correspondence to the previously reported hazard ratios with their composite endpoints: for the TASTE trial, the results were neutral for both the hazard ratio and win odds. The hazard ratio was 0.86 (0.67-1.10), and the win odds were 1.02 (0.99-1.04). Similar results were found for the iFR-SWEDEHEART, DETO2X-AMI, and VALIDATE trials. The IAMI trial showed better results for the vaccinated group compared to the placebo for both the hazard ratio and win odds.

Conclusions: Win statistics offer an alternative approach to traditional survival analysis by harnessing multiple events hierarchically by clinical importance. Win statistics also offer the potential to evaluate a broader range of clinical endpoints, providing a more rounded perspective of treatment efficacy, an important consideration when designing future randomized controlled trials. This is the first multi-registry-based controlled trial reanalysis using win statistics.