Completed Trials Research Articles

Maintenance Therapy Post-Stem Cell Transplantation for Patients with T-Cell Lymphomas.

Given the poor outcomes for peripheral T-cell lymphomas (PTCL), stem cell transplant (SCT) remains an important therapeutic approach. Post-SCT relapse is common and maintenance therapy post-SCT is increasingly being utilized. Here we review the use of post-SCT maintenance therapy for PTCL patients. Maintenance therapy is increasingly utilized to decrease post-SCT relapse and improve outcomes in PTCL. Ongoing and completed post-SCT maintenance trials utilizing agents such as romidepsin, brentuximab vedotin, duvelisib, and pembrolizumab have shown efficacy in decreasing relapse. Further, additional agents with efficacy in PTCL have emerged that may inform future maintenance approaches. Maintenance therapy is a promising approach to maintain response after SCT in PTCL. While several trials are ongoing to evaluate maintenance therapy in PTCL, current data suggests this may be an effective method to decrease post-SCT relapse.

Detection, significance and potential utility of circulating tumor cells in clinical practice in breast cancer (Review).

Although advances in diagnostic techniques, new therapeutic strategies and personalization of breast cancer (BC) care have improved the survival for a number of patients, BC remains a major cause of morbidity and mortality for women. The study of circulating tumor cells (CTCs) has significant potential in translational oncology since these cells represent promising biomarkers throughout the entire course of BC in patients. CTCs also have notable prognostic value in early BC as well as metastatic BC. Based on current knowledge, it seems that the dynamics of CTCs that change during therapy reflect therapy response, and CTCs could serve as a tool for risk stratification and real-time monitoring of treatment in patients with BC. The question of how to use this information in everyday clinical practice and how this information can guide or change therapy to affect the clinical outcome of patients with BC remains unanswered. The present review aims to discuss current completed and ongoing trials that have been designed to demonstrate the clinical significance of CTCs, offer insights into treatment efficacy and assess CTC utility, facilitating their implementation in the routine management of patients with BC.

TARGETED THERAPY IN DIFFUSE INTRINSIC PONTINE GLIOMA: A COMPREHENSIVE REVIEW OF MONOCLONAL ANTIBODIES

Abstract AIMS Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor, marked by its poor prognosis and frequent recurrence despite conventional therapy. Our review examines the molecular landscape of DIPG, highlighting key factors driving tumor progression. We evaluate the therapeutic potential of various monoclonal antibodies (mAbs) targeting these factors, providing insights into their mechanisms and ongoing clinical trials. Our aim is to guide future investigations and immunotherapeutic strategies for DIPG. METHOD A narrative review was conducted using the PubMed database to identify relevant review articles, clinical trials, and observational studies published within the past 10 years, focusing on the use of mAbs in DIPG. The search terms “monoclonal antibodies”, “diffuse intrinsic pontine glioma”, and “targeted therapy” were employed. Additionally, a search was conducted on clinicaltrials.gov to gather information on ongoing and completed clinical trials. RESULTS Current human clinical trials on the checkpoint inhibitors anti-PD-1 (Nivolumab, Pembrolizumab, Balstilimab, Cemiplimab), anti-PD-L1 (Durvalumab), and anti-CTLA-4 (Ipilimumab, Zalifrelimab) have not demonstrated significant improvement in overall patient survival. One major limitation has been the small sample size and limited expression of such markers in DIPG. Conversely, combination therapies involving anti-VEGF (Bevacizumab) and anti-EGFR (Nimotuzumab and Cetuximab) have shown promising results in small sample studies, but these results are not conclusive. Trials on anti-CD276 (Omburtamab) and CD40 agonist (APX005M) have shown no specific clinical or tumor outcomes in DIPG. Newer emerging agents like anti-TIM3 and anti-IL13Ra2 have shown very favorable results in in-vivo and in-vitro studies. CONCLUSION Current evidence is insufficient to support the use of mAbs in DIPG. More large-size studies investigating the combinations of checkpoint inhibitors with different therapeutic agents are needed. Additionally, the promising results seen with anti-VEGF and anti-EGFR mAbs in their respective combination therapies warrant exploration in large-scale studies to draw more accurate conclusions. Furthermore, human trials should be conducted on anti-TIM3 and anti-IL13Ra2.

Combination makes strength: a narrative review of transarterial radioembolization plus immune checkpoint inhibitors for hepatocellular carcinoma.

Immune checkpoint inhibitors (ICIs) and transarterial radioembolization (TARE) are now regarded as promising and versatile therapies for hepatocellular carcinoma (HCC). Combining TARE and ICIs may offer synergistic antineoplastic effects by integrating local and systemic tumor control. This review critically discusses recent preclinical evidence supporting the TARE-ICI combination strategy, completed and ongoing clinical trials, and the challenges in identifying optimal target populations and treatment protocols. A comprehensive literature search was conducted in multiple electronic databases (PubMed, Scopus, and Web of Science) from January 1999 to January 2024. The first part of the search was directed at identifying concluded studies regarding the TARE-ICIs combination. The second part aimed at identifying ongoing clinical trials exploring the Clinicaltrials.gov database. The combination of TARE and ICIs is a promising strategy, supported by preclinical evidence of immune activation post-TARE and potential synergies with ICIs. Early-phase clinical trials have reported encouraging efficacy. However, significant heterogeneity exists among these studies, particularly concerning target populations and treatment schedules. The current evidence on TARE-ICI is favorable and promising in improving outcomes of patients with HCC. Further conclusive and higher levels of evidence are pending.

Trigger Point Injections for Myofascial Pain in Terminal Cancer: A Randomized Trial.

The aim of this study was to evaluate the efficacy and safety of a single trigger point injection (TPI) of a local anesthetic for the treatment of myofascial pain syndrome (MPS) in patients with incurable cancer. This multicenter, exploratory, open-label, randomized comparative trial was conducted in five specialized palliative care departments. Hospitalized patients with incurable cancer who had been experiencing pain related to MPS were randomized to receive either a TPI of 1% lidocaine plus conventional care (TPI group) or conventional care alone (control group). The short-term efficacy and occurrence of adverse events were compared between groups. The primary endpoint was the percentage of patients who experienced a reduction in pain scores of ≥ 50%, assessed using an 11-point Numerical Rating Scale, at 3 days post-intervention. Adverse events were assessed using the Common Terminology Criteria for Adverse Events v5.0. Fifty patients were enrolled, and the trial completion rate was 100%. The proportion of patients who experienced an improvement in Numerical Rating Scale pain scores of ≥ 50% was 70.8% (95% confidence interval, 52.4% to 89.2%) in the TPI group and 0.0% in the control group; the difference was statistically significant (p < 0.001). In the TPI group, one case (4.2%) of Grade 1 nausea and one case (4.2%) of Grade 1 somnolence were reported. A single TPI of a local anesthetic is safe and efficacious in inducing an immediate reduction in MPS-related pain in patients with incurable cancer.

Consideration of factors of low accrual and methods for setting appropriate accrual periods: Japan Clinical Oncology Group study

BackgroundPoor patient accrual can delay reporting of clinical trials and, consequently, the development of new treatments. For reducing the risk of additional resource requirements, a method for setting planned accrual periods with minimal deviation from the actual accrual periods is desirable. Risk factors for poor patient accrual and the appropriate method of estimating the required accrual period for timely completion of clinical trials were evaluated using the data of trials conducted by the Japan Clinical Oncology Group.MethodsThe study included 199 trials that started patient accrual between January 1, 1990, and June 30, 2021. The explanatory variables included factors that could be evaluated prior to trial commencement. We also evaluated whether the estimation methods for accrual pace could lead to completion within the planned accrual period.ResultsApproximately 23.6% of trials were completed within the planned accrual period. The risk factors for trial extension included planned accrual periods > 3 years (reference group: ≤ 3 years, odds ratio [OR] 0.37, 95% confidence interval [CI]: 0.15–0.92, P = 0.033) and stratified trial design (reference group: nonrandomized phase II trials, nonrandomized phase III trial [OR: 3.28, 95% CI: 0.99–10.9, P = 0.051], randomized phase II trial [OR: 3.91, 95% CI: 0.75–20.30, P = 0.105], and randomized phase III trial [OR: 9.29, 95% CI: 3.39–25.40, P < 0.001]). The method of estimating the accrual pace based on past clinical trials facilitated timely completion of the trial (OR: 3.51; 95% CI: 1.73–7.10, P < 0.001), unlike the estimation method based on survey evaluation of the accrual pace for participating institutions (OR: 1.12, 95% CI: 0.56–2.26, P = 0.751). Furthermore, the discrepancy between planned and actual accrual periods was minimal when using the methods of considering the accrual pace of past clinical trials.ConclusionsConsidering the accrual pace of past clinical trials is useful for estimating the required accrual period if data from past trials are available. When conducting a survey, it is necessary to be cautious of overestimating the cases at each facility.

7373 CAM2029, Octreotide Subcutaneous Depot, Provides Sustained Biochemical Control of Acromegaly: Interim Results From a Phase 3 Study (ACROINNOVA 2)

Abstract Disclosure: D. Ferone: Consulting Fee; Self; Camurus AB, Recordati, Novartis-AAA, Ipsen. Grant Recipient; Self; Camurus AB, Recordati, Novartis-AAA, Ipsen. Research Investigator; Self; Camurus AB. J. Silverstein: Consulting Fee; Self; Xeris Pharmaceuticals. Research Investigator; Self; Camurus AB. P. Freda: Research Investigator; Self; Camurus AB. L. Katznelson: Advisory Board Member; Self; Camurus AB, Recordati. F. Gatto: Advisory Board Member; Self; Camurus AB. Research Investigator; Self; Camurus AB. P. Kadioglu: None. P. Maffei: Research Investigator; Self; Camurus AB. J. Seufert: Research Investigator; Self; Camurus AB. J.L. Spencer-Segal: Advisory Board Member; Self; Camurus AB. Research Investigator; Self; Camurus AB. E. Isaeva: None. A. Dreval: None. M. Harrie: Employee; Self; Camurus AB. Stock Owner; Self; Camurus AB. A. Svedberg: Employee; Self; Camurus AB. Stock Owner; Self; Camurus AB. A.M. Pedroncelli: Employee; Self; Camurus AB. Stock Owner; Self; Camurus AB. F. Tiberg: Employee; Self; Camurus AB. Stock Owner; Self; Camurus AB. Background: Acromegaly is characterized by excess growth hormone (GH) and insulin-like growth factor 1 (IGF-1) production. A key treatment goal is long-term biochemical control to minimize adverse effects of prolonged excess GH. CAM2029 is a novel, subcutaneous, octreotide depot, designed for convenient monthly self-administration using a pre-filled injection/pen. In a 24-week Phase 3 trial (ACROINNOVA 1, NCT04076462), CAM2029 achieved superior IGF-1 control vs placebo (IGF-1 ≤ upper limit of normal [ULN]: 72.2 vs 37.5%; P=0.0018) in acromegaly patients previously controlled with standard-of-care (SoC; octreotide long-acting repeatable/lanreotide Autogel). On trial completion, patients could roll over to a Phase 3, 52-week, open-label, long-term safety trial (ACROINNOVA 2, NCT04125836). Here, we report data from an interim analysis of roll-over patients in ACROINNOVA 2. Methods: Roll-over patients received monthly CAM2029 20 mg for 28 weeks in ACROINNOVA 2. Primary endpoint: occurrence of adverse events (AEs). Key secondary endpoints: proportion of patients with available assessments who had (i) IGF-1 ≤1x ULN (mean of weeks 50/52 measurements) and (ii) both IGF-1 ≤1x ULN (weeks 50/52 mean) and mean GH &amp;lt;2.5 µg/L (week 52). Data are reported according to prior treatment in ACROINNOVA 1. Safety data from the whole trial period are reported. Results: Fifty-four of the 64 patients completing ACROINNOVA 1 (prior CAM2029 n=36; prior placebo n=18) entered ACROINNOVA 2. At data cut-off (May 23, 2023) 28 and 15 patients in the prior CAM2029 and prior placebo groups, respectively, had completed treatment week 52; 7 and 3 were ongoing; 1 and 0 had discontinued. The medication was well tolerated with a safety profile comparable to SoC treatment; no new safety signals were observed. One treatment-related serious AE (cholelithiasis, moderate severity, resolved) occurred in the prior placebo group. Injection site treatment-emergent AEs (Grade ≤2) occurred in 50% of patients in the prior CAM2029 (18/36) and prior placebo (9/18) groups. Of evaluable patients in the prior CAM2029 and prior placebo groups, 89.3% (25/28) and 100% (15/15) had IGF ≤1x ULN at weeks 50/52; 88.5% (23/26) and 100% (14/14) had both IGF ≤1x ULN (week 50/52) and GH &amp;lt;2.5 µg/L (week 52). Mean IGF-1 levels remained &amp;lt;ULN throughout the 52-week study period for the prior CAM2029 group; in the prior placebo group, mean IGF-1 increased above 1x ULN during placebo treatment, returning to &amp;lt;ULN after switching to CAM2029 for 28 weeks. All patients previously treated with placebo regained IGF-I control upon switching to CAM2029. Conclusions: The safety profile of CAM2029 was consistent with SoC, with no new or unexpected safety signals during extended treatment. CAM2029 provided persistent control of IGF-1 and GH during 52 weeks of treatment. All patients in the prior placebo group regained biochemical control of acromegaly after switching to CAM2029. Presentation: 6/1/2024

Retraction notice to Gedatolisib Associated Acute Myocarditis in a Patient With Breast Adenocarcinoma: J Am Coll Cardiol. 2024;83(13 Suppl):3575.

The abstract "Gedatolisib Associated Acute Myocarditis in a Patient with Breast Adenocarcinoma" has been retracted at the request of the Editor-in-Chief because it was published before the completion of the clinical trial and full analysis of all data. There are no concerns about the findings as reported. This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal).

Design and Rationale of a Pragmatic Randomized Clinical Trial of Early Dronedarone versus Usual Care to Change and Improve Outcomes in Persons with First-Detected Atrial Fibrillation – The CHANGE AFIB Study

BackgroundWhile there are several completed clinical trials that address treatment strategies in patients with symptomatic and recurrent atrial fibrillation (AF), there are no randomized clinical trials that address first-line rhythm control of new-onset AF. Recent data suggest that early initiation of rhythm control within 1 year can improve outcomes. MethodsIn this open-label pragmatic clinical trial nested within the Get With The Guidelines Atrial Fibrillation registry, approximately 3,000 patients with first-detected AF will be enrolled at approximately 200 sites. Participants will be randomized (1:1) to treatment with dronedarone in addition to usual care versus usual care alone. The primary endpoint will be time to first cardiovascular (CV) hospitalization or death from any cause through 12 months from randomization. Secondary endpoints will include a WIN ratio (all-cause death, ischemic stroke or systemic embolism, heart failure hospitalization, acute coronary hospitalization), CV hospitalization, and all-cause mortality. Patient reported outcomes will be analyzed based on change in Atrial Fibrillation Effect on Quality of Life (AFEQT) and change in Mayo AF-Specific Symptom Inventory (MAFSI) from baseline to 12 months. ConclusionCHANGE AFIB will determine if treatment with dronedarone in addition to usual care is superior to usual care alone for the prevention of CV hospitalization or death from any cause in patients with first-detected AF. The trial will also determine whether initiation of rhythm control at the time of first-detected AF affects CV events or improves patient reported outcomes. ClinicalTrials.gov #- NCT05130268

Poor registration and publication practices in clinical trials of targeted therapeutics for endocrine and metabolic diseases: an observational study

ObjectiveTo assess the completeness and concordance of reporting in registries and corresponding publications of interventional trials on targeted therapeutics for endocrine and metabolic disorders. Study Design and SettingWe searched clinical trial registries in September 2022 for completed interventional trials of target therapeutics for endocrine and metabolic disorders registered from 2005 onwards. We used ClinicalTrials.gov and the World Health Organization International Clinical Trial Registration Platform (WHO ICTRP) registration requirements to extract data and assess the completeness of initial entry and final updates to trial registration and concordance with their published journal articles. ResultsAmong 149 clinical trials included, 121 (81%) had corresponding publications. Missing mandatory registration data items were identified in 88 (67%) trials at the initial registration, 17 (13%) at the last registration, and in 85 (77%) corresponding publications. All trials showed changes between initial registration and final registration update, and 98% showed changes from the initial registration to publication. Changes between initial registration and final update were most common in the categories ‘Completion date’ (92%), ‘Key secondary outcomes’ (82%), and ‘Date of first enrolment’ (70%). Changes between initial registration and publication were most common in categories ‘Sample size’ (91%), ‘Key inclusion and exclusion criteria’ (81%), ‘Key secondary outcomes’ (84%), and ‘Completion date’ (83%). ConclusionDespite the legal and journal registration requirements, the completeness and consistency of reporting mandatory data items in registries and corresponding publications regarding targeted therapeutics for endocrine and metabolic disorders are inadequate. Our findings raise questions about the integrity and reliability of clinical trials focusing on targeted therapeutics.

Is low-intensity shockwave therapy for erectile dysfunction a durable treatment option?-long-term outcomes of a randomized sham-controlled trial.

Low-intensity shockwave therapy (LiSWT) is an emerging non-invasive and restorative therapy for erectile dysfunction (ED) with demonstrated efficacy and few adverse events. Although LiSWT has been shown to improve erectile function amongst men with ED, few studies have examined its long-term durability. We present the long-term results of a randomized controlled trial (RCT) assessing erectile function after LiSWT. A total of 30 patients with baseline ED seen at the University of Virginia were randomized to LiSWT or sham treatment. Patients in the sham group crossed over at 1 month and were unblinded. After initial trial completion, patients enrolled in the long-term outcome study were considered one combined cohort. Patients were treated twice weekly for 3 consecutive weeks with a Storz® Duolith™ device delivering 3,000 shockwaves at 0.1 mJ/mm2 to the distal penis, the base of the penis, and the crura. Primary outcomes were changes in Sexual Health Inventory for Men (SHIM) and Erection Hardness Score (EHS) from baseline (3 months pre-treatment) up to 36 months post-treatment. Changes in SHIM and EHS scores were evaluated using linear mixed effects models. Patient satisfaction was assessed with the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) index. The mean baseline SHIM score was 10.8±0.94. At 12-, 24-, and 36-month assessment following treatment, the mean SHIM scores were 15.6±1.27 (P<0.001), 15.0±1.14 (P<0.001), and 12.2±1.43 (P=0.31). The mean baseline EHS score was 1.87±0.17. At 12-, 24-, and 36-month assessment following treatment, the mean EHSs were 2.70±0.24 (P<0.001), 2.66±0.21 (P<0.001), and 2.29±0.26 (P=0.10). The median [interquartile range (IQR)] EDITS score was 48.9 (22.7, 74.4), indicating moderate satisfaction with LiSWT. There were no adverse events recorded. Our analysis demonstrates sustained long-term improvement in erectile function after LiSWT for a heterogeneous cohort. While limited by population size, the results suggest durable improvement in erectile function for the first 2 years with a peak treatment effect at 1 year. Treatment effect appears to decline between 2 and 3 years. ClinicalTrials.gov, NCT04434352.

Albumin adjuvant therapy for acute ischemic stroke with large vessel occlusion (AMASS-LVO): rationale, design, and protocol for a phase 1, open-label, clinical trial.

Acute ischemic stroke (AIS) is an acute brain injury caused by sudden occlusion of a blood vessel. Endovascular therapy is the most effective way to restore blood flow. However, despite the restoration of blood flow in some patients, their clinical prognosis often remains unsatisfactory. Albumin has shown neuroprotective effects in animal models of AIS. Therefore, this study aims to evaluate the safety, feasibility, and efficacy of local arterial infusions of 20% human serum albumin solution as an adjuvant therapy after endovascular therapy in patients with AIS. This study is a prospective, therapeutic exploratory, non-randomized, open-label, phase 1 clinical trial testing the use of 20% human serum albumin solution injected via the artery immediately after successful reperfusion in patients with AIS. The study is divided into two stages. In the first stage, a single-dose-finding will explore the maximum safe dose according to the 3 + 3 dose escalation principle;, with the maximum dose being 0.60 g/kg. After recanalizing the occluded blood vessel, human serum albumin solution will be injected into the internal carotid artery region through a guiding catheter for 30 min. The second stage involves an albumin adjuvant therapy cohort (AT) and an endovascular treatment lonely cohort (ET). The AT cohort will encompass at least 15 additional participants to complete safety trials at the maximum safe dose determined in the first stage. The ET cohort will include well-matched patients receiving endovascular therapy alone, derived from a contemporaneous prospective registry, who will be excluded from having cardiopulmonary disorders and from receiving any neuroprotective therapy. The primary outcome of this study will be symptomatic intracranial hemorrhage. Efficacy outcomes will include the proportion of patients with the progression of cerebral infarction volume, a modified Rankin Scale of 0-2 on day 90 after randomization. An exploratory secondary outcome will be the analysis of thromboinflammatory and neuroprotective molecule profiles. This pilot trial aims to explore the safety and efficacy of arterial infusion of an albumin solution after occlusive vessel opening in AIS. The results will provide data parameters for subsequent tests on the arterial infusion of albumin solutions. ClinicalTrials.gov, NCT05953623.

The OBS UK Dashboard: an interactive tool for representative trial site selection to facilitate equality and diversity in maternity research

BackgroundObstetric Bleeding Study UK (OBS UK) (award ID: 152057) is a National Institute for Health and Care Research (NIHR)-funded stepped wedge cluster randomised controlled trial of a complex intervention for postpartum haemorrhage. This was developed in Wales and evaluated in a feasibility study, with improvements in maternal outcomes observed. Generalisability of the findings is limited by lack of control data and limited ethnic diversity in the Welsh obstetric patient population compared to the United Kingdom (UK): 94% of the Welsh population identifies as White, versus 82% in the UK. Non-White ethnicity and socioeconomic deprivation are linked to increased risk of adverse maternal outcomes. Traditionally, decisions regarding site selection are based on desire to complete trials on target in ‘tried and tested’ research active institutions. To ensure widespread applicability of the results and investigate the impact of ethnicity and social deprivation on trial outcomes, maternity units were recruited that represent the ethnic diversity and social deprivation profiles of the UK.MethodUsing routinely collected, publicly available data, an interactive dashboard was developed that demonstrates the demographics of the population served by each maternity unit in the UK, to inform site recruitment. Data on births per year, ethnic and socioeconomic group of the population for each maternity unit, across the UK, were integrated into the dashboard.ResultsThe dashboard demonstrates that OBS UK trial sites reflect the ethnic and socioeconomic diversity of the UK (study vs UK population ethnicity: White 79.2% vs 81.7%, Asian 10.5% vs 9.3%, Black 4.7% vs 4.0%, Mixed 2.5% vs 2.9%, Other 3.0% vs 2.1%) with variation in site demography, size and location. Missing data varied across sites and nations and is presented.ConclusionThe NIHR equality, diversity and inclusion strategy states studies must widen participation, facilitating individuals from all backgrounds to engage. The development of this novel interactive dashboard demonstrates an innovative way of achieving this. National Health Service (NHS) maternity researchers should consider using this tool to enhance diversity in research, address health disparities and improve generalisability of findings. This approach could be applied to healthcare settings beyond maternity care and across different global populations.Trial registrationISRCTN 17679951. Registered on August 30, 2023.

Reporting and communication of sample size calculations in adaptive clinical trials: a review of trial protocols and grant applications

BackgroundAn adaptive design allows modifying the design based on accumulated data while maintaining trial validity and integrity. The final sample size may be unknown when designing an adaptive trial. It is therefore important to consider what sample size is used in the planning of the study and how that is communicated to add transparency to the understanding of the trial design and facilitate robust planning. In this paper, we reviewed trial protocols and grant applications on the sample size reporting for randomised adaptive trials.MethodWe searched protocols of randomised trials with comparative objectives on ClinicalTrials.gov (01/01/2010 to 31/12/2022). Contemporary eligible grant applications accessed from UK publicly funded researchers were also included. Suitable records of adaptive designs were reviewed, and key information was extracted and descriptively analysed.ResultsWe identified 439 records, and 265 trials were eligible. Of these, 164 (61.9%) and 101 (38.1%) were sponsored by industry and public sectors, respectively, with 169 (63.8%) of all trials using a group sequential design although trial adaptations used were diverse.The maximum and minimum sample sizes were the most reported or directly inferred (n = 199, 75.1%). The sample size assuming no adaptation would be triggered was usually set as the estimated target sample size in the protocol. However, of the 152 completed trials, 15 (9.9%) and 33 (21.7%) had their sample size increased or reduced triggered by trial adaptations, respectively.The sample size calculation process was generally well reported in most cases (n = 216, 81.5%); however, the justification for the sample size calculation parameters was missing in 116 (43.8%) trials. Less than half gave sufficient information on the study design operating characteristics (n = 119, 44.9%).ConclusionAlthough the reporting of sample sizes varied, the maximum and minimum sample sizes were usually reported. Most of the trials were planned for estimated enrolment assuming no adaptation would be triggered. This is despite the fact a third of reported trials changed their sample size. The sample size calculation was generally well reported, but the justification of sample size calculation parameters and the reporting of the statistical behaviour of the adaptive design could still be improved.

The role of molecular biomarkers in recurrent glioblastoma trials: an assessment of the current trial landscape of genome-driven oncology

For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments.

Trial Factors Associated With Completion of Clinical Trials Evaluating AI: Retrospective Case-Control Study.

Evaluation of artificial intelligence (AI) tools in clinical trials remains the gold standard for translation into clinical settings. However, design factors associated with successful trial completion and the common reasons for trial failure are unknown. This study aims to compare trial design factors of complete and incomplete clinical trials testing AI tools. We conducted a case-control study of complete (n=485) and incomplete (n=51) clinical trials that evaluated AI as an intervention of ClinicalTrials.gov. Trial design factors, including area of clinical application, intended use population, and intended role of AI, were extracted. Trials that did not evaluate AI as an intervention and active trials were excluded. The assessed trial design factors related to AI interventions included the domain of clinical application related to organ systems; intended use population for patients or health care providers; and the role of AI for different applications in patient-facing clinical workflows, such as diagnosis, screening, and treatment. In addition, we also assessed general trial design factors including study type, allocation, intervention model, masking, age, sex, funder, continent, length of time, sample size, number of enrollment sites, and study start year. The main outcome was the completion of the clinical trial. Odds ratio (OR) and 95% CI values were calculated for all trial design factors using propensity-matched, multivariable logistic regression. We queried ClinicalTrials.gov on December 23, 2023, using AI keywords to identify complete and incomplete trials testing AI technologies as a primary intervention, yielding 485 complete and 51 incomplete trials for inclusion in this study. Our nested propensity-matched, case-control results suggest that trials conducted in Europe were significantly associated with trial completion when compared with North American trials (OR 2.85, 95% CI 1.14-7.10; P=.03), and the trial sample size was positively associated with trial completion (OR 1.00, 95% CI 1.00-1.00; P=.02). Our case-control study is one of the first to identify trial design factors associated with completion of AI trials and catalog study-reported reasons for AI trial failure. We observed that trial design factors positively associated with trial completion include trials conducted in Europe and sample size. Given the promising clinical use of AI tools in health care, our results suggest that future translational research should prioritize addressing the design factors of AI clinical trials associated with trial incompletion and common reasons for study failure.

Modulating energy metabolism to treat non-obstructive hypertrophic cardiomyopathy? Insights from IMPROVE-HCM.

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease worldwide and may present with or without dynamic left ventricular outflow tract obstruction (LVOTO). Significant advances have been made in the management of obstructive HCM. On the other hand, despite their significant symptomatic burden, patients with non-obstructive HCM (nHCM) (i.e., without LVOTO) still do not have evidence-based therapeutical options. The recent IMPROVE-HCM study, a phase 2 randomized, double-blinded trial, aims to place a first step in filling this gap in knowledge. The study assessed the safety (primary endpoint) and efficacy (secondary endpoint) of ninerafaxstat, a novel cardiac mitotrope drug that increases adenosine triphosphate production. We highlighted the main findings of the trial, contextualizing these results within the larger landscape of completed and ongoing trials in nHCM.

Effect of leech therapy in dermatophytosis: A randomized standard controlled trial

Background and purposeIn Unani medicine leech therapy is used as analgesic and resolvent purposes. The saliva of leech contains various biological substances like Hirudin, hyaluronidase, vasodilators, anesthetics, antibacterial, fibrinases, collagenase etc. To compare the efficacy of Leech therapy with local antifungal clotrimazole (1 %) cream in dermatophytosis on long term basis. Material and methodsA randomized, standard controlled, open labeled, clinical study was conducted on 40 patients of dermatophytosis, aged 18–60 years, and were randomly assigned into two groups; 20 patients in test group and 20 in control group. Patients were diagnosed clinically and confirmed through KOH examination. Complete haemogram, bleeding and clotting times, random blood sugar, HIV I & II, and HBsAg tests were carried out before starting the therapy, while haemogram was repeated after completion of treatment too. In test group, five sittings of leech therapy were applied, with intervals of one week. The control group was given clotrimazole (1 %) cream for topical application twice daily, continuously for a period of 28 days. Post-treatment follow-ups were done on 35th day in person, and then over the phone on 45th, 60th, and 90th days. Data were collected using Signs and Symptoms Severity Score for study, and Visual Analogue Scale (VAS). After completion of trial, appropriate tests were applied for statistical analysis of data. ResultsThe study shows, in most of the parameters, statically significant therapeutic effect in both the groups (p<0.001). No patients of either group reported any adverse event throughout the trial. Conclusionit appeared that leech therapy can contribute significantly in treating dermatophytosis (Qūbā) without any adverse effect, and with prolonged efficacy compared to standard treatment.

AI-assisted 3D analysis of grasping and reaching behavior of squirrel monkeys during recovery from cervical spinal cord injury

We have previously demonstrated that machine learning-based video analysis, conducted via DeepLabCut, is more sensitive for detecting subtle deficits in hand grasping behavior than traditional end-point performance assessments. This superiority was observed in a nonhuman primate (NHP) model of cervical spinal cord injury, specifically a dorsal column lesion (DCL). The current study aims to further characterize the kinematic aspects of the deficits in hand reaching, grasping, and retrieving behavior from a 3D perspective following a DCL. Squirrel monkeys were trained to retrieve sugar pellets from eight wells, which were located either on a flat plate or a raised tube with varying well depths. This setup was designed to require coordinated finger movements during the task. Immediately after the DCL, the animals exhibited measurable behavioral deficits. These were characterized by significant increases in grasping speed squared and trial completion time, markedly widened movement trajectories of individual fingers, and abnormalities in inter-finger distance and orientation. Increased task difficulty was associated with more pronounced behavioral deficits. By three months post-DCL, video-based measurements indicated no significant recovery, even though global end-point performance had returned to baseline levels. Our findings demonstrate that deprivation of tactile information results in impaired dexterous hand behavior involving coordinated finger movements, and the impairment is sustained for 20 weeks. This spinal cord injury (SCI) model, along with DeepLapCut analysis, provides a valuable platform for separately evaluating sensory and motor functions and their contributions to dexterous hand behavior and may be used for evaluating therapeutic interventions using more sensitive behavioral outcome readouts.

PSLBI-21 Interactive effects of dietary betaine supplementation and soybean hulls inclusion on growth performance and carcass composition of young growing pigs

Abstract Growing barrow pigs [n = 24; Large White x Landrace x Duroc; 29.51 ± 3.24 kg initial body weight (BW)] were assigned to 4 treatments in a 2 x 2 factorial design to evaluate the synergistic effects of dietary levels of betaine (BET; 0 and 0.1%) and soybean hulls (SBH; 0 and 15%) on growth performance and carcass composition. Pigs were blocked by initial BW and housed in individual pens with ad libitum access to feed and water for a 28-d feeding period. Pigs were weighed and feed intake was recorded at 14-d intervals. Real-time ultrasonic (RTU) measurements of the 10th-rib longissimus dorsi muscle area (LMA) and off-midline backfat thickness (BF) were obtained initially and on d 28 for all pigs. Prediction equations were used to estimate total fat tissue (TOFAT) and fat-free total lean (FFTOLN) from the measurements. All data were analyzed using the MIXED procedure of the SAS software. Growth performance data were analyzed as repeated measures on time and carcass data were analyzed as single measures with the respective baseline values used as covariate in the statistical model. There were no SBH x BET interactions for growth response variables. Pig growth was not affected by dietary BET supplementation. During the first 14 d of the study, pigs fed 15% SBH had decreased average daily gain (ADG; P = 0.01), average daily feed intake (ADFI; P = 0.02), and feed efficiency [gain:fee; (G:F;P = 0.04)] when compared with pigs fed diets without SBH. From d 15 to 28, dietary addition of 15% SBH reduced ADFI (P = 0.01), whereas no significant effects on the other growth performance variables were observed. Overall, when compared with pigs fed diets without SBH, pigs fed diets with 15% SBH had reduced feed intake (P = 0.01) and ADG (P = 0.04), which resulted in lighter pigs (P = 0.03) at the completion of the feeding trial. A SBH x BET interaction (P = 0.04) was observed for LMA, with decreased values (P &amp;lt; 0.05) detected for BET-supplemented pigs only when SBH was not included in the diet. No additional carcass composition traits were altered by BET supplementation. Including 15% SBH to the diet decreased BF (P = 0.05) and TOFAT (P = 0.04) in growing pigs. Neither BET supplementation nor SBH inclusion affected FFTOLN. In conclusion, adding supplemental BET to diets with SBH did not synergistically alter nutrient partitioning of young growing pigs. Although no beneficial effects of BET supplementation on growth and carcass composition traits were observed, feeding pigs diets containing 15% SBH resulted in slower growth rates with less fat deposition.