Secondary lower extremity lymphoedema is a chronic progressive condition that frequently develops after cancer treatment and results in persistent swelling, recurrent cellulitis and impaired quality of life. Lymphaticovenous anastomosis (LVA) is an established physiological microsurgical treatment; however, postoperative outcomes vary and evidence-based adjunctive postoperative management remains limited. A novel pneumatic lymphatic drainage (PLD) system has been developed to deliver anatomically directed, pathway-aligned mechanical stimulation that mimics manual lymphatic drainage. Its clinical efficacy following LVA has not yet been evaluated in a randomised controlled trial.

This multicentre, open-label, parallel-group randomised controlled trial will enrol adults (≥18 years) with unilateral secondary lower extremity lymphoedema (International Society of Lymphology stage I–II) undergoing LVA. Participants will be randomised 1:1 to receive PLD plus standard postoperative care or standard postoperative care alone. PLD will be initiated on the day of surgery and continue for 6 months (Day 183). The primary outcome is the rate of improvement in excess limb volume (EV) at Day 183 relative to baseline, calculated from circumferential measurements taken at 4 cm intervals using the truncated cone method, with the contralateral limb serving as an internal control. Secondary outcomes include longitudinal trajectories of EV, improvement in excess limb fluid volume assessed by bioimpedance, the Lymphedema Quality of Life Questionnaire, cellulitis incidence and safety outcomes. A total of 64 participants (32 per group) will provide 80% power (two-sided α=0.05) to detect a 15-percentage-point between-group difference in the rate of improvement in EV at 6 months, assuming a common SD of 20 percentage points and allowing for attrition. Primary analyses will follow the ITT principle using mixed-effects models for repeated measures.

The study was approved by the Chiba University Certified Review Board (approval number: CRB0119-25; approval date: 15 December 2025) and was conducted in accordance with the Declaration of Helsinki and the Japanese Clinical Trials Act. Results will be disseminated through peer-reviewed publications and presentations at national and international scientific conferences, irrespective of study outcomes.

jRCTs032250600.

Chronic central serous chorioretinopathy (CSC) can cause progressive and permanent vision loss. Although photodynamic therapy (PDT) is a primary treatment option globally, it is not approved for CSC worldwide, limiting therapeutic access. The REPLAY trial is a phase III, investigator-initiated trial to evaluate the efficacy and safety of reduced-fluence PDT (rf-PDT) for chronic CSC to seek the first regulatory approval globally.

This study comprises two cohorts. The ‘untreated cohort’ is a multicentre, randomised, placebo-controlled, double-masked trial involving 60 patients with untreated, fovea-involving chronic CSC, randomised 2:1 to receive a single rf-PDT or placebo treatment. The ‘previously treated cohort’ is a single-arm, open-label trial for up to 10 patients with recurrent CSC after PDT. The primary endpoint for both cohorts is the proportion of eyes with a complete resolution of subfoveal fluid at 12 weeks post-treatment, assessed by optical coherence tomography. Secondary endpoints include changes in best-corrected visual acuity, central choroidal thickness, recurrence rates and incidence of adverse events over a 48 week follow-up.

The study protocol was approved by the Kyoto University Hospital Institutional Review Board, IRB of Chiba University Hospital, Tokyo Women’s Medical University Institutional Review Board and Institutional Review Board of Kansai Medical University Hospital. Written informed consent is obtained from all participants. The results will be disseminated through publication in a peer-reviewed journal and presentations at scientific conferences.

jRCT2051230156 (URL: https://jrct.mhlw.go.jp/latest-detail/jRCT2051230156).

Guided parent-delivered cognitive behavioural therapy (GPD-CBT) is an evidence-based, low-burden treatment programme for childhood anxiety disorders with demonstrated efficacy, cost-effectiveness and accessibility. However, it has been tested primarily in Western countries, and the efficacy and cost-effectiveness have not been evaluated in Japanese families. The current study aims to examine GPD-CBT’s efficacy and cost-effectiveness in Japanese samples and explore potential cultural adaptations of the programme.

This study is designed as a Bayesian single-blind randomised controlled trial with two parallel groups: GPD-CBT (intervention group) and a waitlist control group. The primary outcome is remission of primary anxiety disorders evaluated through diagnostic interviews by independent evaluators. Secondary outcomes include child and parent-reported child anxiety symptoms, depressive symptoms and life interference. Additionally, measures of parental psychological characteristics, programme acceptability and quality of life are collected. We will conduct qualitative interviews with parents who participated in the programme and therapists who delivered the intervention to explore potential cultural adaptations. We aim to recruit 54–170 families, depending on the results of sequential Bayesian analyses. GPD-CBT consists of seven weekly 20 min sessions and a 1-month follow-up session. Assessments will be conducted at baseline, 13 weeks post randomisation (primary endpoint for between-group comparison), with an additional 25 weeks post randomisation. The waitlist control group will receive GPD-CBT after the 13-week assessment.

This study has been approved by the Ethics Review Committees of Chiba University and the University of Tokyo. We will disseminate results through academic conference presentations and peer-reviewed journal publications. If the GPD-CBT intervention proves efficacious, we will promote wider implementation in Japan through the development of training programmes for mental health professionals and key stakeholders.

jRCT1032250421 (https://jrct.mhlw.go.jp/latest-detail/jRCT1032250421) and jRCT1030250422 (https://jrct.mhlw.go.jp/latest-detail/jRCT1030250422) registered on 9 October 2025.

The effect of prophylactic clipping for colorectal cold snare polypectomy (CSP) on delayed bleeding (DB) in patients with antithrombotic drugs remains unverified. The aim of the PERCOLD study is to demonstrate the non-inferiority of DB rates in cases without prophylactic clips compared with cases with prophylactic clips in patients taking antithrombotic drugs for colorectal CSP through randomised controlled trial (RCT).

This study is a multicentre prospective parallel-group RCT phase 3 trial that is being conducted at 14 institutions in Japan at the time of writing this manuscript. After providing consent, patients will undergo screening and assessment for study enrolment eligibility. Patients taking antithrombotic drugs (aged 20 years or older at the time of consent and who have agreed to participate in this study) will be selected if they have a preoperative suspected adenoma (including sessile serrated lesion) with an endoscopic diameter of

The trial protocol has been approved by the Chiba University Certified Clinical Research Reviewer Board (CRB3180015), which serves as the central ethics committee, and registered with Japan Registry of Clinical Trials. The current protocol V.1.7, dated 4 October 2024. Written informed consent for participation in the study will be obtained from all participating patients. All participating institutions have formally agreed to conduct the study in accordance with this central approval, and local site permissions were obtained as required by each institution. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences.

Japan Registry of Clinical Trials (jRCT1032230086).

Neonatal haemochromatosis, considered to be a gestational alloimmune liver disease (NH-GALD), is a rare but serious disease that results in fulminant hepatic failure. The recurrence rate of NH-GALD in a subsequent infant of a mother with an affected infant is 70%–90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) therapy has been reported as being effective for preventing recurrence of NH-GALD in a subsequent infant. However, no clinical trial has been conducted to date.

This is a multicentre open-label, single-arm study of antenatal maternal high-dose IVIG therapy in pregnant women with a history of documented NH in a previous offspring. The objective of this study is to evaluate the efficacy and safety of antenatal maternal high-dose IVIG therapy in preventing or reducing the severity of alloimmune injury to the fetal liver.

The clinical trial is being performed in accordance with the Declaration of Helsinki. The trial protocol was approved by the Clinical Research Review Board at four hospitals. Before enrolment, written informed consent would be obtained from eligible pregnant women. The results are expected to be published in a scientific journal.

28 October 2024, V.8.0.

jRCT1091220353.

Ischaemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide. Despite strong recommendations, the implementation rate of outpatient cardiac rehabilitation (CR) in Japan remains low. Mobile health technologies, such as Personal Health Record (PHR) applications combined with wearable devices, may enhance adherence to rehabilitation programmes. This study aims to evaluate the effectiveness of a continuous support programme that integrates a PHR app and counselling services in improving the continuation rate of outpatient CR and exercise tolerance in patients with IHD.

This is a single-blind randomised controlled trial with a parallel-group design. A total of 72 participants with IHD will be recruited from the outpatient departments of Maebashi Red Cross Hospital, Gunma Saiseikai Maebashi Hospital, Okayama University Hospital, Okayama Red Cross Hospital, Momoyama-kai Ono Internal Clinic, Hiroshima University Hospital, Tshuyama Jifu-kai Tsuyama Chuo Hospital and Shinpu-kai Tamashima Chuo Hospital. Participants will be randomly allocated to either the intervention group, which will receive a wearable device, a PHR app, counselling services and a rehabilitation notebook, or the control group, which will receive a wearable device and a rehabilitation notebook without the PHR app and counselling. The primary outcome is the change in peak oxygen uptake from baseline to 150 days. Secondary outcomes include changes in anaerobic threshold, number of outpatient rehabilitation visits, daily steps and vital signs. Data will be analysed using a generalised estimating equations for primary outcomes and appropriate statistical tests for secondary outcomes, following an intention-to-treat approach.

Ethical approval for this study was obtained from the ethics committee of the Kyoto University Graduate School and Faculty of Medicine (C1669-1). In addition, permission to conduct the study was granted by the director of each participating institution. Participants will provide informed consent prior to participation. Findings will be disseminated through peer-reviewed journals, conferences and summary reports to stakeholders.

This trial is registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (trial identifier: UMIN000055823).