Advancements in Managing Anthracycline-Induced Cardiotoxicity: Insights from Interventional Clinical Trials

Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS=LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35±5.03vs. 25.04±4.10, p<.001), LVGLS (-22.77±2.45vs. -20.44±2.62, p<.001), and LAVGLS (51.12±5.63vs. 45.61±5.22, p<.001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30±4.73vs. 57.08±5.83, p<.001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of>19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC),.842; p<.001), a ΔLVGLS of>13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC,.763; p<.001), and a ΔLAVGLS of>16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC,.905; p<.001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905vs..763, p=.027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9%vs. 74.2%, p=.002) and maintained sensitivity in predicting LV cardiotoxicity. LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.

Introduction: According to Regulation (EC) 536/2014, clinical trials (CTs) of medicinal products (MPs) in humans may be conducted to detect or confirm the clinical, pharmacological, or pharmacodynamic effects of one or more investigational medicinal products (IMPs), to determine adverse drug reactions, or to study absorption, distribution, metabolism, and excretion to establish their safety and/or efficacy. Aim: Analysis of data provided by the International Clinical Trials Registry Platform. Materials and Methods: We conducted a document and content analysis of the International Clinical Trials Registry Platform, as well as the World Health Organization (WHO) standards for registration of clinical trials. Results and Discussion: In 2006, the WHO established the International Clinical Trials Registry Platform, which aims to make information on clinical trials publicly available. The platform brings together data from ClinicalTrials.gov as well as nineteen other clinical trial registries around the world. EudraCT (European Union Drug Regulatory Authorities Clinical Trials Database) is the European database for all interventional clinical trials on medicinal products. The Clinical Trials Information System (CTIS) supports the interaction between clinical trial sponsors, EU Member States, and EEA countries. According to data from the WHO platform, the total number of clinical trials registered worldwide for the period 1999-2022 is 744,100, of which 577,531 are interventional. The largest number of interventional clinical trials were registered in the USA, followed by China, Japan, and Germany. Eighty-nine thousand sixty-nine of the registered clinical trials were for malignancies and forty-five thousand forty-eight for cardiovascular diseases. Adult patients were included in 72% of the trials and children in 11%. Conclusion: The WHO platform aims to improve access to information on clinical trials and promotes ethical research practices. We identified the utility of using multiple clinical trial databases to perform a comprehensive analysis.

Keeping the Heart Fitm2 during Chemotherapy.

Introduction and purpose: Anthracyclines are highly effective chemotherapeutic agents but carry a significant risk of dose-dependent cardiac toxicity, often progressing silently before left-ventricular ejection fraction (LVEF) declines. The objective of this review was to evaluate the role of three-dimensional echocardiography (3D-ECHO) and global longitudinal strain (GLS) in the early detection of subclinical anthracycline-induced cardiotoxicity and to compare their diagnostic performance with conventional 2D-LVEF assessment. Methods: A narrative review was conducted using clinical and observational studies indexed in PubMed over the last ten years. Only peer-reviewed human research evaluating anthracycline-induced cardiotoxicity was included. Studies comparing 2D-LVEF with 3D-LVEF and/or global longitudinal strain (GLS), as well as those assessing early markers of subclinical left-ventricular dysfunction, were selected. Extracted data focused on diagnostic effectiveness, time-to-detection of myocardial injury, and prognostic relevance of strain-based parameters. Conclusion: GLS and 3D-echocardiography outperform conventional 2D-LVEF in identifying early, subclinical anthracycline-related cardiotoxicity. GLS provides the highest sensitivity for early myocardial injury, while 3D-STE enhances spatial assessment and detects dysfunction before EF decline. Routine integration of these modalities into cardio-oncology surveillance may enable earlier intervention, prevent irreversible damage, and improve long-term cardiac outcomes.

Aims/IntroductionDiabetic peripheral neuropathy (DPN) is the most common complication of diabetes. At present, there is no comprehensive summary of the clinical trials related to DPN. In this article, we summarized the basic characteristics of the interventional clinical trials pertaining to DPN to determine the current status of research in this field and the existing issues.Materials and MethodsWe searched the World Health Organization International Clinical Trial Registration Platform (ICTRP), PubMed and Web of Science for clinical trials from 2005 to April 2021 and extracted 149 registered and 459 published clinical trials on DPN. We summarized the characteristics of the clinical trials, including the source registration, recruitment status, stage, age group, allocation method, intervention, end point classification, funding source, and treatment.ResultsAfter excluding noninterventional and nontreatment trials, 149 registered clinical trials out of 292 records from 12 registration centers and 459 published articles were included in this study. Among the registered trials, 43% had been completed, and 34.4% had been published in peer-reviewed journals. Among these trials, more than half used random allocation and blinded placebo-controlled methodologies. A total of 40.3% of the trials were multicenter studies, 63.8% of the treatments were drug therapies, and the endpoint classifications of 49% were efficacy and safety. Of the 459 published interventional clinical trials on DPN, 69.7% of the trials used drug treatments; more than half were randomized, double-blind, placebo-controlled clinical trials; 94.1% had positive outcomes; 46.4% had a target size of 50; and 22.9% were multicenter.ConclusionThis paper systematically summarizes the current status of interventional trials on DPN registered in the ICTRP and published clinical trials and provides a reference for the development of high-quality intervention strategies for DPN in the future.

Cardiac side effects associated with anthracycline-based treatment may seriously compromise the prognosis of patients with breast cancer (BC). Evidence shows that genes that operate in drug metabolism can influence the risk of anthracycline-induced cardiotoxicity (AIC). ATP-binding cassette (ABC) transporters could serve as one of the potential biomarkers for AIC risk stratification. We aimed to determine the link between single-nucleotide polymorphisms (SNPs) in several ABC genes (ABCB1 rs1045642, ABCC1 rs4148350, ABCC1 rs3743527) and cardiotoxicity. The study included 71 patients with BC, who were treated with doxorubicin-based chemotherapy. Two-dimensional echocardiography and speckle-tracking echocardiography were performed. AIC was defined as a new decrease of 10 percentage points in the left ventricular ejection fraction (LVEF). SNPs in ABCB1 and ABCC1 genes were evaluated using real-time PCR. After a cumulative dose of 236.70 mg/m2 of doxorubicin, 28.2% patients met the criteria of AIC. Patients who developed AIC had a larger impairment in left ventricular systolic function compared to those who did not develop AIC (LVEF: 50.20 ± 2.38% vs. 55.41 ± 1.13%, p < 0.001; global longitudinal strain: -17.03 ± 0.52% vs. -18.40 ± 0.88%, p < 0.001). The ABCC1 rs4148350 TG genotype was associated with higher rates of cardiotoxicity (TG vs. GG OR = 8.000, 95% CI = 1.405-45.547, p = 0.019). The study showed that ABCC1 rs4148350 is associated with AIC and could be a potential biomarker to assess the risk of treatment side effects in patients with BC.

Establishing transparency to restore trust in clinical trials

Finding the road to recovery: therapeutic and clinical trial implications of dysfunctional viable myocardium in heart failure with reduced ejection fraction.

Objective: To analyze clinical trials of traditional medicine (including Chinese herbal medicine and nonpharmacological therapies) for the treatment of type 2 diabetes mellitus (T2DM) registered in the International Clinical Trials Registry Platform (ICTRP), and accordingly to explore their clinical trial registration characteristics, development trend and intervention status, in an attempt to provide references for future research design, diagnosis and management of traditional Chinese medicine therapy for T2DM. Methods: The clinical trials related to Chinese herbal medicine and nonpharmacological therapies for treating T2DM were retrieved on the ICTRP online from the time of database construction to August 13, 2023, to analyze the time of registration, country and institution of the study, source of funding, type and design of the study, randomization and blinding methods, clinical staging, therapeutic measures, and main therapeutic effect indexes. Descriptive statistical analysis was performed using R4.3.0 and Excel software. Results: A total of 774 clinical trials for T2DM treatment were included, of which 127 were traditional herbal therapies and 647 were nonpharmacological therapies. The T2DM clinical trial registration institutions were distributed in 50 countries worldwide involving 15 clinical registration platforms, with the most registrations in Iran, China, and Australia, and the top 3 registration platforms were the Iranian Clinical Trial Registry, the Australian New Zealand Clinical Trials Registry, and the ICTRP. Universities (551, 71.19%) were the main funding sources. Intervention studies (750, 96.90%) were the primary study type, including randomized controlled trials (432, 56. 4%), and 225 studies mentioned the blinding method. A total of 530 (68.48%) with a sample size ≤100 were included. Study phases were predominantly phase 2 and phase 3 (108, 51.43%). The interventions of traditional medicine for T2DM were composed of Chinese herbal medicines (mainly ginseng and astragalus compound), nonpharmacological therapies (mainly exercise and diet therapies), and 2 or more comprehensive treatment regimes. According to the type of study design, the first 3 main therapeutic indexes were fasting blood glucose (286 times), glycated hemoglobin (282 times), and insulin resistance (120 times), and the top 3 secondary therapeutic indexes were body mass index (179 times), fasting blood glucose (175 times), and glycated hemoglobin (134 times). Conclusion: The study dissects the current status and trend of registration of clinical trials on traditional medicine for T2DM treatment. The number of trial registrations is on the rise year by year, and there are obvious geographical differences in the countries and platforms of registration. The trial design is mainly randomized controlled blind trials with a sample size of &lt;100, and the main interventions are nonpharmacological therapies. Correct and standardized registration of clinical trials and timely reporting of study results are greatly important to facilitate the implementation of clinical trials, reduce publication bias, provide high-level diagnostic and therapeutic bases for clinical practice guidelines, and develop effective treatment strategies. This study is expected to help other scholars, health care professionals, patients, and the public to understand the latest research trends and hotspots in this field and provide certain references and inspirations for the future research design and clinical practice of traditional Chinese medicine in the treatment of T2DM.

Registration of clinical trials

Leprosy is a neglected tropical disease of public health importance. Although Africa carries a substantial share of the global leprosy burden, there is only limited evidence for African patients based on leprosy-related clinical trials. This scoping review aims to map existing evidence on the involvement of African patient populations in leprosy-related clinical treatment, prophylaxis and vaccine trials. A scoping review was performed in 2023 by two independent reviewers following the PRISMA guideline. The electronic databases PubMed and Infolep, and clinical trial registries (Cochrane CENTRAL, WHO International Clinical Trials Registry Platform) were systematically searched for past and ongoing clinical trials on leprosy with recruitment in Africa up to 31 December 2022. 16 trials were registered on the WHO platform, but none had published results. Predefined data points were extracted, and study quality was assessed using Cochrane's RoB2 and ROBINS-I tools. The review is registered in PROSPERO. Out of 198 publications, 22 were eligible for extraction, representing 18 clinical trials. The majority of trials were conducted in Malawi, Ethiopia and Uganda. 12 trials focused on treatment, 2 on vaccines, 3 on treatment reactions and 1 on prophylaxis. 10 clinical trials were randomized, 14 were controlled and 6 trials were blinded. One of these trials was pseudo-randomized and, therefore, not considered as randomized. Dapsone was the most frequently studied drug. 15 (83%) of all identified studies were conducted before the year 2000 having one study that published one paper before 2000 and one after 2000. 11 studies were assessed with the RoB2 tool and 8 (73%) showed high risk of bias. One study with two publications showed one serious and one medium risk of bias. Among 7 studies assessed with the ROBINS-I tool, 2 (29%) showed a serious risk of bias. This scoping review demonstrates the substantial under-representation of the African patient population in leprosy clinical trials and highlights the low volume and a decrease in clinical trial conduct since the year 2000. To address this imbalance and improve the relevance of trial outcomes, there is a critical need to engage local stakeholders and build research capacities in Africa. These efforts will be essential for more inclusive and effective leprosy interventions.

In 2005, the International Committee of Medical Journal Editors (ICMJE) initiated a policy requiring investigators to deposit information about trial design into an accepted clinical trials registry before the onset...

Time to adopt a new standard method for assessing cardiac function in chemotherapy-induced cardiotoxicity in breast cancer? A systematic review and meta-analysis.

Mitigating Administrative Risks in Industry-sponsored Clinical Trials

In this response, we will interpret ‘‘epidemiological’’ as ‘‘observational studies’’, and ‘‘clinical intervention’’ studies as ‘‘randomised studies’’. A prototype epidemiological study would be a cohort study, and a prototype clinical intervention study