General fatigue in patients with long COVID is a major medical issue in primary care. Since there is a lack of evidence-based treatments, Japanese traditional (Kampo) medicine has gained attention in Japan. However, there has been no study to evaluate the efficacy of Japanese traditional medicine. This study aimed to evaluate the efficacy of hochuekkito (Bu-Zhong-Yi-Qi-Tang) in long COVID patients with general fatigue. The primary objective of this study is to assess whether the Japanese traditional (Kampo) formulation, hochuekkito, effectively alleviates general fatigue associated with long COVID. Designed as a randomised, double-blind, placebo-controlled trial, the study involves participants who, after providing written informed consent, are allocated to one of two treatment arms: arm A (hochuekkito) or arm B (placebo). The intervention will last for 6 weeks, during which treatment assignment remains concealed from both study personnel and participants. The primary measure of efficacy is the score on the Japanese version of the Fatigue Assessment Scale (FAS) evaluated at the 6-week post-intervention mark. The target sample size is 156 participants, divided equally into two arms of 78 patients each. Recruitment commenced in December 2024 and is expected to conclude by December 2026. General fatigue is the most frequent symptom of long COVID and is often treated by primary care physicians. Long COVID limits the social life of those afflicted. The goal of this project is to demonstrate a treatment for long COVID general fatigue with a high level of evidence. Japan Registry of Clinical Trials (jRCT), trial registration: jRCTs061240010 (https://jrct.mhlw.go.jp/latest-detail/jRCTs061240010), registered on 15th May 2024.
Many people with a physical health condition are ineligible for randomised clinical trials (RCTs) of treatments for that condition. However, less is known about the differences in characteristics and outcomes between those that are eligible and ineligible for RCTs. Systematic review without meta-analysis. Screened studies were those included in a previous review of trial eligibility (full-text rescreened for this study) and new studies identified in a Medline and Embase search from 12/02/18 to 13/04/23. Included studies were those which evaluated the proportion of patients in a real-world population eligible for one or more RCTs, which additionally compared eligible and ineligible patient characteristics. Titles and abstracts were screened by two reviewers independently and risk of bias assessed. Comparisons were demographic/clinical characteristics and outcome rates in real-world data (RWD). Median differences were compared using Wilcoxon signed rank. Forty-nine studies examining 122 trials in 52 RWD sources were included. 34/49 studies examined cardiovascular trials (57/122 trials), seven examined cancer (30 trials), two musculoskeletal diseases (24 trials) and two respiratory diseases (11 trials). Risk of bias was high for 33 (67.3
HIV-1 infection is controllable with antiretroviral therapy (ART); however, HIV-1 cure remains elusive. Despite ART, people with HIV-1 (PWH) face increased morbidity and mortality, requiring long-term treatment. A growing body of evidence demonstrates the central nervous system (CNS) is an HIV-1 reservoir representing a barrier to HIV-1 eradication. HIV-1 DNA is found in brain tissue from PWH on suppressive ART, with multiple reports of CNS virologic escape. Despite suppressive ART, HIV-1 RNA and anti-HIV-1 antibodies have been detected in cerebrospinal fluid (CSF). We have performed extensive preclinical and clinical work on the Janus kinase (Jak) 1/2 inhibitor drug class to target HIV-1, including baricitinib, an FDA-approved treatment for acute COVID-19, rheumatoid arthritis, and alopecia areata. Our studies with Jak 1/2 inhibitors demonstrate inhibition of (1) HIV-1 replication, (2) HIV-1-induced activation and infection in the CNS, and (3) reservoir lifespan, size, and reactivation. Peripheral administration of baricitinib decreased CNS HIV-1 burden, markers of HIV-1 persistence, and reversed behavioral abnormalities associated with HIV-1-induced inflammation in a murine model of CNS HIV-1 infection. Here, we describe our phase IIa trial of baricitinib to decrease the HIV-1 CNS reservoir in PWH exhibiting durable virologic suppression on ART. This is a phase IIa randomized, double-blind, placebo-controlled trial in individuals aged 18–64 years with well-controlled HIV-1 receiving ART. The study will randomize 64 participants to receive oral baricitinib 2 mg/day or placebo for 10 weeks. The primary outcome is change in HIV-1 CNS reservoir. Secondary outcomes include inflammatory quantifications (neuroimaging, blood, and CSF) and neuropsychological performance. Our primary hypothesis is that individuals receiving baricitinib will be more likely to achieve a change in CSF integrated proviral DNA (IPDA). Secondary hypotheses include baricitinib treatment will be associated with a significant decrease in other markers of HIV-1 CNS persistence (CSF cell-associated viral DNA, CSF viral RNA, CSF HIV-1 Tat, CSF and blood markers of inflammation, and magnetic resonance imaging markers). Additionally, we hypothesize baricitinib treatment will improve neurocognitive performance, depressive symptoms, and neuronal damage markers. We expect this study will provide strong rationale for inclusion of baricitinib in future trials targeting eradication of HIV-1. The trial was registered at ClinicalTrials.gov NCT05452564 on 06 July 2022 at URL https://clinicaltrials.gov/study/NCT05452564.
Abstract Background Recent studies have demonstrated significant benefits associated with prehabilitation prior to major surgery. However, digital solutions in this domain are currently lacking. Our previous study, the Protego Maxima trial, reported positively assessed usability, validity, and safety of a prehabilitation application. In this randomized-controlled multicenter study, we aim to ascertain whether a digital prehabilitation program can reduce perioperative morbidity and costs in patients undergoing major surgery. Methods The LUMOS trial is a multicenter prospective randomized-controlled trial comparing a 3-to-6-week interventional digital prehabilitation program with a digitized informational app, against a control group receiving only the informational application. The trial seeks to enroll 382 participants who will be block-randomized based on diagnosis into either the intervention or control group. The primary endpoint is the reduction of 90-day morbidity from 60 to 45% (Dindo–Clavien I–V). Secondary objectives include the 1-year overall survival, quality of life, length of hospital stay (including ICU, IMC, and general ward), readmission rates, compliance, and program adherence, product malfunction, vigilance reporting, improvement of the 6-min walking test by at least 20%, and hospital cost assessment. Discussion The LUMOS trial aims to evaluate the effectiveness of a digital prehabilitation program compared to an informational app only, prior to major surgery. The objective is to demonstrate the significant value of a digitized remote prehabilitation program in reducing perioperative morbidity, as well as addressing cost considerations. Trial registration Trial registered in the European Database on Medical Devices (EUDAMED) (CIV-24-02-046162) and German Clinical Trial Registry (DRKS00033612, 13.05.2024), DMIDS-Number: 00015083, https://drks.de/search/en/trial/DRKS00033612 . Goethe University Frankfurt: 024-1681-MDR/MPDG-zuständig multizentrisch, 06.05.2024.
The COVID-19 pandemic disrupted clinical research worldwide, but its impact on the conduct of large international trials in neurocritical care is not well documented. We aimed to assess how the pandemic affected recruitment, consent processes, patient characteristics, and outcomes in the HEMOTION trial, a randomized study comparing liberal and restrictive transfusion strategies in patients with traumatic brain injury (TBI). We conducted a post-hoc observational analysis of the HEMOTION trial. Adults with moderate-to-severe TBI (Glasgow Coma Scale ≤12) and hemoglobin ≤10 g/dL were randomized to liberal (transfusion triggered by a hemoglobin level ≤10 g/dL) or restrictive (transfusion triggered by a hemoglobin level ≤7 g/dL) transfusion strategy. Patients enrolled between September 1, 2017, and April 13, 2023, were compared according to two periods: before the pandemic (Sep 2017–Jan 2020) and during the pandemic (Feb 2020–Apr 2023). The main outcomes of this analysis were screening and recruitment rates and the proportion of consent refusals. Other outcomes included transfusion practices, neurologic outcome at 6 months (Glasgow Outcome Scale–Extended, GOS-E), mortality, quality of life, and hospital-acquired infections. Statistical analyses used nonparametric and hierarchical models. Among 736 trial participants, 203 were recruited before and 533 during the pandemic. Patients enrolled during the pandemic presented with lower Glasgow Coma Scale (GCS) motor scores (median 4 [IQR, 1–5] vs 4 [IQR, 2–5]; p=0.02) and longer time from injury to randomization (60 h [IQR, 41–91] vs 49 h [IQR, 30–78]; p=0.001). Screening rates (p=0.004) and recruitment rates (0.21 [IQR, 0.13–0.29] vs 0.29 [IQR, 0.17–0.57] patients/center/15 days; p=0.01) were lower during the pandemic. Consent refusals increased (28.2
