Journal of clinical trials最新文献

Objective: The COVID-19 pandemic led to immediate changes in cancer clinical trial conduct. The primary aims of this study were to summarize the impact of the pandemic on Alliance for Clinical Trials in Oncology (Alliance) enrollment, protocol deviations, COVID-19 events (positive or presumptive-positive COVID test), and premature study discontinuation rates.

Methods: Enrollment trends were examined from January 2019 (pre COVID-19 pandemic) through 2022. Data were captured for protocol deviations and premature treatment and study discontinuation events across all Alliance protocols using a centralized Medidata Rave database, and summarized from January 1, 2020, through June 30, 2022. Descriptive statistics and graphical techniques are used to summarize observed trends.

Results: Overall enrollment across Alliance trials decreased during the COVID-19 pandemic and remained below pre-pandemic levels in 2022. Racial and ethnic demographics of enrolled patients did not change substantially. 4805 protocol deviations were reported on 2745 unique patients, with at least one protocol deviation reported by 618 sites and 77 unique trials. Commonly reported deviations were telemedicine visits (n=2167, 45%) and late/missed study procedures (n=2150, 45%). A total of 826 COVID-19 events were reported in 659 unique patients. Of an estimated 18,000 enrolled patients, only 68 withdrew from treatment and 45 withdrew from study due to COVID-19.

Conclusion: A centralized COVID-19 database enabled a comprehensive assessment of the impact of the pandemic across Alliance trials. COVID-19 led to an immediate decline in enrollment across all patient populations. While the number of trials open to patient accrual remained stable, several large, adjuvant studies completed accrual during this period, which contributed to accrual decline. Telemedicine usage was notable, and both COVID-19 events and study discontinuation due to COVID-19 were rare.

Background: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children. MMF is rapidly converted to the biologically active metabolite mycophenolic acid (MPA) whose pharmacokinetics (PK) is characterized by large inter- and intra-individual variability.

Methods/design: This randomized, double-blind, active comparator, controlled clinical trial of pediatric subjects with proliferative LN compares pharmacokinetically-guided precision-dosing of MMF (MMF_PK, i.e. the dose is adjusted to the target area under the concentration-time curve (AUC_0-12h) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMF_BSA, i.e. MMF dosed 600 mg/m² body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMF_PK or MMF_BSA for up to 53 weeks. The primary outcome is partial clinical remission of LN (partial renal response, PRR) at week 26, and the major secondary outcome is complete renal response (CRR) at week 26. Subjects in the MMF_BSA arm with PRR at week 26 will receive MMF_PK from week 26 onwards, while subjects with CRR will continue MMF_BSA or MMF_PK treatment until week 53. Subjects who achieve PRR at week 26 are discontinued from study intervention.

Discussion: The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) study will provide a thorough evaluation of the PK of MMF in pediatric LN patients, yielding a head-to-head comparison of MMF_BSA and MMF_PK for both safety and efficacy. This study has the potential to change current treatment recommendations for pediatric LN, thereby significantly impacting childhood-onset SLE (cSLE) disease prognosis and current clinical practice.

Introduction: Erectile Dysfunction (ED) is a common challenge post Radical Prostatectomy (RALP), affecting men's sexual health after undergoing definitive cancer therapy. Despite employing nerve-sparing techniques, ED remains a prevalent issue in this population. Studies indicate that approximately 70%-85% of men experience varying degrees of ED following RALP. The existing treatment landscape for post-RALP-ED presents limitations, and a discernible knowledge gap persists. To address this, our study aims to investigate the efficacy of Shockwave Therapy (SWT) as a potential intervention for managing ED after RALP.

Methods: This prospective, randomized, sham-controlled clinical trial aims to recruit 189 eligible patients post-RP and assess the effects of SWT. Comprehensive screening, including medical history, physical examinations, and biochemical evaluations, will be conducted to confirm eligibility. The intervention involves utilizing a device to administer focal shockwaves targeted at cavernosal tissue. Safety measures include continuous monitoring for adverse events and rigorous reporting protocols. The primary endpoint assesses changes in participants' ability to engage in penetrative intercourse from baseline to study completion, while secondary endpoints encompass various measures of erectile function, including questionnaire-based assessments, ultrasound parameters, and clinical outcomes.

Results: Statistical analysis, encompassing ANOVA for continuous variables and Fisher's exact test for categorical ones, will evaluate demographic characteristics, baseline data, and primary as well as secondary outcomes for statistical significance. Detailed analysis of trends, subgroup comparisons, and treatment effects will provide a comprehensive understanding of the impact of SWT on post-RP ED.

Conclusion: This study protocol represents a rigorous investigation into the potential therapeutic role of SWT in managing post-RP ED. The outcomes from this study aim to contribute valuable insights into the efficacy, safety, and potential improvements in erectile function following SWT, providing significant guidance for future interventions aimed at addressing this challenging condition affecting men's health and quality of life.

Introduction: The SARS-CoV-2 pandemic has spurred the development of numerous Point of Care (POC) immunoassays. Previous studies assessing performance of these available kits occurred in a laboratory setting, raising concerns of translating findings for POC use. We aim to assess the performance of a lateral flow immunoassay for the detection of SARS-CoV-2 antibodies using samples collected at POC.

Method: One lateral flow immunoassay (Humasis® COVID-19 IgG/IgM) was tested. Fifty PCR RT-PCR positive and 52 RT-PCR negative samples were collected at POC. Fifty Pre-Covid serum specimens were used as controls. Clinical data including symptom onset date was collected from patient history and the medical record.

Results: The overall sensitivity for the kit was 74% (95% CI: 59.7%-85.4%). The sensitivity for IgM and IgG detection >14 days after date of onset was 88% (95% CI: 68.8%-97.5%) and 84% (95% CI: 63.9%-95.5%), with a Negative Predictive Value (NPV) of 94% for IgM (95% CI: 83.5%-98.8%) and 93% for IgG (95% CI: 81.8%-97.9%). The overall specificity was 94% (95% CI: 83.5%-98.8%). The Immunoglobulin specific specificity was 94% for IgM (95% CI: 83.5%-98.8%) and 98% for IgG (95% CI: 89.4%-100.0%).

Discussion and conclusion: Humasis® COVID-19 IgG/IgM LFA demonstrates greater than 90% NPV for samples collected 14 days after the onset of symptoms using samples collected at POC.