Clinical Trial Sites Research Articles

A Pilot Study on the Collection of Adverse Event Data from the Patient Using an Electronic Platform in a Cancer Clinical Trial Unit.

Accurate and robust adverse event (AE) data collection is crucial in cancer clinical trials to ensure participant safety. Frameworks have been developed to facilitate the collection of AE data and now the traditional workflows are facing renewal to include patient-reported data, improving completeness of AE data. We explored one of these workflows in a cancer clinical trial unit. The study was a single-site study conducted at a tertiary hospital located in Australia. Patients consenting to a clinical trial were eligible for inclusion in this study. Participants used an electronic platform-My Health My Way (MHMW)-to report their symptomatic data weekly for 24 weeks. A symptom list was included within the platform, along with a free text field. Data reported via the platform was compared with data recorded in the patient's medical chart. Time taken to compile data from each source was recorded, along with missing data points. Agreement between patient-reported data and data recorded in the medical notes was assessed using Kappa and Gwet's AC1; time taken to compile data and missing data points were assessed using a Wilcoxon signed rank test. Low agreement was found between patient- and clinician-reported data (-0.482 and -0.159 by Kappa and Gwet's AC1 respectively). Only 127 (30%) of the total 428 AEs were reported by both MHMW and medical notes. Patients reported higher rates of symptoms from the symptom list, while clinicians reported higher rates of symptoms outside of the symptom list. Time taken to compile the data from MHMW was significantly less than that taken to review medical notes (2.19min versus 5.73min respectively; P < 0.001). There were significantly less missing data points from the MHMW data compared with the medical notes (1.4 versus 7.8; P<0.001). This study confirms previous reports that patient- and clinician-reported adverse event data show low agreement. This study also shows that clinical trial sites could significantly reduce the work performed by research staff in the collection of adverse event data by implementing an electronic, patient-reported platform.

Medical Science Liaisons: A Guide for Advanced Practice Registered Nurses

Medical science liaisons (MSLs) are part of the field medical affairs (FMA) department of pharmaceutical companies and are scientific resources for advanced practice registered nurses (APRNs). Following strict regulations and antikickback statutes, MSLs operate differently from sales and engage in unbiased, nonpromotional scientific exchange to provide clinical resources to APRNs. They also collaborate with shareholders like professional organizations, clinical trial sites, and academic institutions. Understanding MSL engagement allows APRNs multiple avenues both externally and within the pharmaceutical industry to leverage their experience to enhance clinical practice.

Differential patient travel burden to pediatric atopic dermatitis clinical trial sites.

Differential patient travel burden to pediatric atopic dermatitis clinical trial sites.

From hurdles to high performance: overcoming day-to-day challenges for successful clinical trials at sites

Randomized clinical trials are fundamental in testing new drugs, medical devices and treatment protocols. They help to determine the efficacy and safety of new treatments, leading to medical innovations that can significantly improve treatment outcomes. Clinical trial sites are the engines that drive medical advancements, but they face numerous challenges in their day-to-day operations and impact the study outcome as well as data quality. Continuous improvement through research and innovation ensures that clinical trials are conducted more effectively, leading to better healthcare advancements and patient outcomes. Execution of clinical trial at the hospital site is a critical task and associated with the new challenges every day which may include patient recruitment, retention and compliance to the data collection. GCP compliance is a soul of clinical research and difficult task to comply with. GCP is a harmonized guideline accepted by most of the countries all across the globe.

SARS-CoV-2 RNAemia as a reliable predictor of long-term mortality among older adults hospitalized in pulmonary intermediate care units: a prospective cohort study

BackgroundSARS-CoV-2 viremia is associated with disease severity and high risk for in-hospital mortality. However, the impact of SARS-CoV-2 viremia on long-term outcomes in hospitalized patients with COVID-19 is poorly understood.MethodsWe conducted a prospective cohort study and recruited a group of older adult patients with COVID-19 admitted to pulmonary intermediate care units of Peking University Third Hospital during December 2022 and January 2023. The plasma level of SARS-CoV-2 RNA was determined by a standardized RT-PCR technique, and SARS-CoV-2 RNAemia was defined as a plasma viral load ≥ 50 copies/ml. In-hospital and follow-up (180-day) outcome data were collected.ResultsA total of 101 patients with an average of 80.4 years were recruited, and 63.4% of them were severe or very severe cases. Twenty-eight patients (27.7%) had SARS-CoV-2 RNAemia, with a median viral RNA load of 422.1 [261.3, 1085.6] copies/ml. Patients with SARS-CoV-2 RNAemia were more likely to develop critical cases and had a higher incidence of sepsis. Accordingly, they had a higher 180-day mortality (57.1% vs. 19.7%, P < 0.001), as well as in-hospital mortality (50.0% vs. 13.7%, P < 0.001), independent of age, disease severity, sepsis, lymphocyte count and C-Reactive protein. In addition, the risk for 180-day mortality increased with the SARS-CoV-2 RNA load in plasma. Plasma cytokines, including IL-6, IL-8 and IL-10, were higher in patients with SARS-CoV-2 RNAemia.ConclusionsOur study indicates that SARS-CoV-2 RNAemia serves as a useful biomarker for predicting mortality, especially long-term mortality, in older adult patients hospitalized in pulmonary intermediate care units.Trial registrationChinese Clinical Trial Registry website (No. ChiCTR2300067434).

Acute Effects of Citrulline Malate Supplementation on Nocturnal Blood Pressure Dipping After Exercise in Hypertensive Patients: A Randomized, Placebo-Controlled Trial

Background Citrulline malate (CM), especially when used in conjunction with physical exercise, has demonstrated potential as a non-pharmacological adjunct in the management of hypertension. Nevertheless, its impact on nocturnal blood pressure dipping remains unexplored. Objective Evaluate the impact of a single dose of CM on nocturnal blood pressure dipping after exercise in hypertensive individuals. Methods In a double-blind, placebo-controlled, parallel-group clinical trial, twenty hypertensive adults (55 ± 16 years) were randomly assigned to either a CM (6 g) or placebo (6 g of corn starch) group (PLA). Resting blood pressure was measured after a 20-min period of comfortable seating in a calm environment. Both groups underwent 40 min of treadmill running/walking at an intensity of 60–70% of their reserve heart rate, 120 min after ingesting the substances. Ambulatory blood pressure monitoring was employed to measure blood pressure over 24 h. Results No significant differences in systolic blood pressure values were observed between the CM and PLA groups at rest, during wakefulness, sleep, or over a 24-h period. However, CM exhibited a significant reduction in diastolic blood pressure in several metrics: delta 24 h (-14 mmHg vs −6 mmHg, p = 0.047), delta wakefulness (-12 mmHg vs −4 mmHg, p = 0.024), percent delta 24 h (-16% vs −6%, p = 0.024), and percent delta wakefulness (-14% vs −4%, p = 0.013). No significant differences were found between CM and PLA in terms of systolic and diastolic nocturnal absolute reductions (-13 mmHg vs −12 mmHg, p = 0.808, and −13 mmHg vs −8 mmHg, p = 0.273, respectively) or nocturnal percentage decrease (-9.9% vs −9.4%, p = 0.844, and −15.3% vs −11.7%, p = 0.399, respectively). Conclusions The study found no significant changes in the post-exercise nocturnal blood pressure dip following a single dose of CM supplementation. However, a notable reduction in diastolic blood pressure was observed during the waking period and over the average 24-h monitoring period. Clinical trial registry number and website ClinicalTrials.gov platform (NCT03378596).

Validating claims-based algorithms for a systemic lupus erythematosus diagnosis in Medicare data for informed use of the Lupus Index: a tool for geospatial research

ObjectiveThis study aimed to validate claims-based algorithms for identifying SLE and lupus nephritis (LN) in Medicare data, enhancing the use of the Lupus Index for geospatial research on SLE prevalence...

Racial representation in multicenter clinical trials leading to drug approvals for gynecological cancer indications by the US Food and Drug Administration (FDA).

66 Background: Enrollment disparities in gynecologic (Gyn) cancer clinical trials in the United States (US) are well-documented. However, there is limited data evaluating how recruitment sites in international clinical trials contribute to racial representation, specifically in Gyn cancers. Here, we examined racial enrollment and geographic location in clinical trials that have led to approval for Gyn cancer applications. Methods: Agents approved by the FDA for Gyn cancer treatment and corresponding clinical trials were identified from the FDA Drug Approvals and Databases. Enrollment data were abstracted from ClinicalTrials.gov then cross-checked with published manuscripts and FDA labels. Using Gyn disease site prevalence from the 2021 SEER database, we calculated expected enrollment proportions by race and compared these to actual clinical trial enrollment data. The binomial test was used to compare expected vs. observed proportions with White patients as the reference group. Results: From 2014 to 2024, 9 drugs received 22 FDA approvals for ovarian (n=13), endometrial (n=4), or cervical cancer (n=5). These approvals were based on 28 clinical trials enrolling a total of 13,763 patients (75.7% White, 3.4% Black, 12.0% Asian, 8.9% Other/Unknown). These trials included 1 (3.6%) US only study, 3 (10.7%) non-US, primarily Europe-based studies (PAOLA-1, AURELIA, STUDY42 [Europe + Australia]), and 24 (85.7%) international studies across the US and 46 other countries. Considering the distribution of race (White: 86.3%, Black: 8.4%, Asian: 4.9%) of Gyn cancers in the US, Black patients had lower enrollment (45% of expected enrollment) vs. White patients (95% of expected enrollment, P&lt;0.0001). African countries were rarely included among the recruitment sites. Two international trials reported patient recruitment from South Africa (3.2% Black, 6/188 patients, 38% of expected enrollment).However, Asian patients had higher enrollment (269% of expected enrollment, P&lt;0.0001) compared to White patients. In 13 trials that included study sites in East Asia, Asian patients comprised 16% of the trial population (1310/8205 patients; 327% of expected enrollment) vs. 3.2% in trials that did not open in Asia (n=15) (181/5558 patients; 67% of expected enrollment). Conclusions: Black patients were underrepresented in pivotal trials that led to FDA approvals for Gyn cancers. Overrepresentation of Asian patients was likely due to international enrollment from East Asia. Post-marketing retrospective studies or additional studies focused on underrepresented groups are needed to assess true drug efficacy and safety in US populations that are disproportionately affected by Gyn cancer mortality.

Efficacy and safety of spleen aminopeptide oral solution for children with allergic rhinitis and adenoid hypertrophy: a randomised trial.

The spleen aminopeptide oral solution (SAOS) is a solution containing a mixture of polypeptide amino acids and polynucleotides derived from healthy bovine spleen. This study aimed to establish a randomized controlled clinical trial to evaluate the efficacy and safety of SAOS for children with allergic rhinitis (AR) and adenoid hypertrophy (AH). Children with AR and AH who visited the Otolaryngology Department of the Children's Hospital Affiliated with Fudan University between June 2022 and April 2023 were included. The primary outcome was the adenoid-to-nasopharynx (A/N) ratio, and the secondary outcomes included nasal symptom score, AH score, and medication score. The primary outcome was evaluated before treatment (T0), after 1 month of treatment (T1), and after 2 months of treatment (T2). Blood and urine samples were collected at T0 and T2 for safety evaluation. A total of 78 patients were included, with 36 in the control group and 42 in the SAOS group. As the duration of medication increased, there was a significant decrease in nasal symptom scores (sneezing: F=52.806, P<0.001; runny nose: F=28.802, P<0.001; nasal itching: F=101.272, P<0.001; nasal congestion: F=83.349, P<0.001). Significant improvements in mouth breathing (Z=-2.650, P=0.008) and restless sleep (Z=-2.759, P=0.006) were observed in the SAOS group compared to the control group at T2. Additionally, the difference in scores between T2 and T0 was significantly lower in the SAOS group compared to the control group (Z=-2.299, P=0.02). As an adjuvant therapy for 8 weeks, SAOS could significantly reduce the size of adenoids and improve clinical symptoms associated with AH. The study was registered on the Chinese Clinical Trial Registry website (https://www.chictr.org.cn/) (registration number: ChiCTR2200056763).

Training to Increase Minority Enrollment in Lupus Clinical Trials With Community Engagement: Enhancing Lupus Clinical Trial Recruitment Through Provider and Community Health Worker Engagement.

This study evaluates the effectiveness of the Training to Increase Minority Enrollment in Lupus Clinical Trials with Community Engagement (TIMELY) program on enhancing referrals of underrepresented patients to lupus clinical trials. TIMELY leverages two existing American College of Rheumatology online educational initiatives: Materials to Increase Minority Involvement in Clinical Trials (MIMICT), a continuing medical education activity for health care providers, and the community health worker (CHW) Lupus Clinical Trials Training (LuCTT). TIMELY introduced a unique roundtable meeting format to build on the existing online educational programs and facilitate discussions between local clinical trial sites and provider and CHW participants. This study used an online pretest and posttest design to assess changes in theory-based behavioral predictors of lupus clinical trial referrals and engagement (ie, knowledge, attitudes, self-efficacy, and intentions) among providers and CHWs. Participants completed MIMICT or LuCTT and then were eligible to participate in roundtable meetings. Paired t-tests were used to assess changes in composite scores before and after the intervention for each of the outcomes. The final sample included 40 providers and 18 CHWs. Knowledge scores increased significantly for both providers (P < 0.01) and CHWs (P < 0.001) on completion of MIMICT and LuCTT, respectively. After participating in the TIMELY roundtable, providers' composite scores for self-efficacy and intentions significantly increased (P < 0.001). Provider self-efficacy gains were sustained at three months' follow-up (P < 0.001). These promising findings highlight the potential and opportunities for the TIMELY program to improve behavioral predictors of trial referrals, including CHW knowledge and providers' knowledge, self-efficacy, and intentions to refer underrepresented patients to lupus clinical trials.

Pharmacokinetics, Safety, and Immunogenicity of a Biosimilar of Nivolumab (LY01015): A Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Trial in Healthy Chinese Male Subjects.

Nivolumab (Opdivo®) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab. This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo®) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed. A randomized, double-blind, parallel-controlled, phase I trial was conducted with 176 healthy male adults receiving a single intravenous infusion of LY01015 or nivolumab at 0.3mg/kg. Pharmacokinetics, safety, and immunogenicity were evaluated over a 99-day period. The primary pharmacokinetics endpoint was AUC0-∞, and the secondary pharmacokinetic endpoints included AUC0-t and Cmax. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00-125.00%. This study is the first to report on the pharmacokinetics, safety, and immunogenicity of Opdivo® in healthy individuals. The pharmacokinetics profiles of LY01015 and Opdivo® were found to be comparable. The geometric mean ratios (90% confidence intervals) for the AUC0-∞, AUC0-t, and Cmax of LY01015 to Opdivo® were 94.49% (90.29-98.88%), 94.92% (88.73-101.54%), and 96.55% (93.32-99.90%), respectively, falling within the conventional bioequivalence criteria of 80.00-125.00%. The safety and immunogenicity were also comparable between the two groups. LY01015 demonstrated highly similar pharmacokinetics to nivolumab in healthy Chinese male subjects. Both drugs exhibited comparable safety and immunogenicity profiles. This trial is registered at the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/ #ChiCTR2200064771).

Efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis in adolescents: A systematic review and meta-analysis of randomized controlled trials.

To assess the efficacy and safety of upadacitinib in adolescents with moderate-to-severe atopic dermatitis (AD). A comprehensive search was conducted using PubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases, spanning from their inception until February 18, 2024. The review incorporated all randomized controlled trials examining upadacitinib's efficacy in managing moderate to severe AD among adolescent patients. The methodological quality of the selected studies underwent thorough assessment utilizing the Cochrane systematic review methodology. Statistical analyses of the outcome measures were executed employing the Review Manager 5.3 software. The meta-analysis encompassed 4 studies in total. Compared to placebo, upadacitinib at doses of both 15 and 30 mg was associated with a significant enhancement in the eczema area and severity index-75% ([odds ratio, OR = 11.06, 95% confidence interval, CI (6.78-18.04), P < .00001]; [OR = 21.73, 95% CI (12.73-37.11), P < .00001]), a reduction in the numerical rating scale of ≥4 ([OR = 6.16, 95% CI (3.56-10.64), P < .00001]; [OR = 10.58, 95% CI (6.12-18.29), P < .00001]), and improvement in the investigator's global assessment to 0/1 ([OR = 8.85, 95% CI (4.86-16.10), P < .00001]; [OR = 21.43, 95% CI (11.64-39.46), P < .00001]). Regarding safety, upadacitinib at both 15 and 30 mg doses was linked to a statistically significant rise in the overall incidence of adverse events when juxtaposed with placebo ([OR = 1.57, 95% CI (1.01-2.44), P = .04]; [OR = 2.21, 95% CI (1.44-3.41), P = .0003]). Nevertheless, no statistically significant disparity was discovered in the occurrence of serious adverse events between upadacitinib and placebo ([OR = 1.02, 95% CI (0.27-3.84), P = .98]; [OR = 0.42, 95% CI (0.09-1.93), P = .26]). The findings from this meta-analysis indicate that upadacitinib demonstrates substantial effectiveness and tolerability in treating moderate to severe AD in adolescents. Moreover, upadacitinib provides a rapid reduction in pruritus and markedly ameliorates symptoms and signs, with the 30 mg dosage showing a more pronounced therapeutic effect relative to the 15 mg dosage.

Association Between State Medicaid Policies and Accrual of Black or Hispanic Patients to Cancer Clinical Trials.

It is unknown whether Medicaid expansion under the Affordable Care Act (ACA) or state-level policies mandating Medicaid coverage of the routine costs of clinical trial participation have ameliorated longstanding racial and ethnic disparities in cancer clinical trial enrollment. We conducted a retrospective, cross-sectional difference-in-differences analysis examining the effect of Medicaid expansion on rates of enrollment for Black or Hispanic nonelderly adults in nonobservational, US cancer clinical trials using data from Medidata's Rave platform for 2012-2019. We examined heterogeneity in this effect on the basis of whether states had pre-existing mandates requiring Medicaid coverage of the routine costs of clinical trial participation. The study included 47,870 participants across 1,353 clinical trials and 344 clinical trial sites. In expansion states, the proportion of participants who were Black or Hispanic increased from 16.7% before expansion to 17.2% after Medicaid expansion (0.5 percentage point [PP] change [95% CI, -1.1 to 2.0]). In nonexpansion states, this proportion increased from 19.8% before 2014 (when the first states expanded eligibility under the ACA) to 20.4% after 2014 (0.6 PP change [95% CI, -2.3 to 3.5]). These trends yielded a nonsignificant difference-in-differences estimate of 0.9 PP (95% CI, -2.6 to 4.4). Medicaid expansion was associated with a 5.3 PP (95% CI, 1.9 to 8.7) increase in the enrollment of Black or Hispanic participants in states with mandates requiring Medicaid coverage of the routine costs of trial participation, but not in states without mandates (-0.3 PP [95% CI, -4.5 to 3.9]). Medicaid expansion was not associated with a significant increase in the proportion of Black or Hispanic oncology trial participants overall, but was associated with an increase specifically in states that mandated Medicaid coverage of the routine costs of trial participation.

Efficacy of Dichrostachys Glomerata Supplementation on Overweight and Mildly Obese Adult’s Weight, Mood, and Health-Related Quality of Life: A Randomized Double-Blind Placebo-Controlled Trial

Despite their widespread use, research is needed to evaluate the weight loss and related health/wellness outcomes of herbal plants. Preliminary research found that the fruit of Dichrostachys glomerata is safe and has potential weight loss effects. This study aimed to examine the effect of a standardized powder of D. glomerata fruit pods (DYG-400®) on weight, food cravings, mood, and health-related quality of life of overweight and mildly obese adults. In this CONSORT-compliant double-blind placebo-controlled trial, 56 adults (Mean [M] age = 44.50, M [body mass index] BMI = 31.66) were randomized to either the D. glomerata Group (DG; 300 mg/d) or Placebo Group (PG; rice protein, 300 mg/d) for 60 days. Participants weight was assessed along with self-report assessments of the Food Cravings Questionnaire, CDC Health-related Quality of Life, Perceived Stress Scale, Trait Anxiety Inventory, and Profile of Mood States at Baseline, Day 30, and Day 60. The data were collected from March 2023 to June 2023 and stored electronically, and analyzed using general linear models with repeated measures. DG lost more weight at Day 60 compared to PG, p = .05 (4.11 vs. 2.19 lbs). DG had reduced food cravings from Baseline to Day 30 and Day 60 compared to PG, p < .001. Perceived stress, p < .001, and mood, p = .017, improved from Baseline to Day 60 for DG compared to PG. Anxiety decreased from Baseline to Day 60 for DG and from Baseline to Day 30 for PG, p < .001. Health-related Quality of Life improved for DG compared to PG, p < .001. D. glomerata (DYG-400®) may be an effective herbal intervention to promote weight loss and health. Extended clinical trials across diverse populations and settings are needed. Clinical trial registry number and website: ISRCTN10099861, https://doi.org/10.1186/ISRCTN10099861.

Exploring Demographic Representation and Reporting in Lung Cancer Clinical Trials with Canadian Sites from 2013 to 2023.

This review evaluates the reporting of demographic characteristics and the diversity of participants of phase III lung cancer clinical trials with Canadian research sites. A literature search was conducted using the ClinicalTrials.gov registry to identify clinical trials conducted between 1 January 2013, and 31 December 2023. The demographic reporting practices and the representation of sex/gender, racial, and ethnic groups were assessed. The location of Canadian research sites was also examined for trends in reporting and representation. Associated publications were reviewed for demographic data collection methods. Of the 25 clinical trials, 24 reported race and 18 also reported ethnicity. All clinical trials reported sex/gender, and the city and province of the participating Canadian sites. Most participants were White (66.1%), identified as not Hispanic or Latino (81.4%), and were male (57.8%). The provinces with the most clinical trial sites were Ontario (43.6%) and Quebec (34.2%). Lung cancer clinical trials lack adequate demographic reporting and representation of females, diverse patient groups, and geographical locations in Canada with high lung cancer incidence rates. Specifically, the Indigenous Peoples of Canada and Nunavut require better representation in lung cancer clinical trials conducted in Canada. These findings highlight the need to improve diversity and demographic representation in clinical research.

Prevention of Recurrent Spontaneous Preterm Delivery Using Probiotics (Clostridium butyricum, Enterococcus faecium, and Bacillus subtilis; PPP Trial): Protocol for a Prospective, Single-Arm, Nonblinded, Multicenter Trial.

The rate of recurrent spontaneous preterm delivery (sPTD) ranges between 27% and 34% and is 22.3% in Japan. Although it currently remains unclear whether probiotics prevent sPTD, retrospective studies recently reported a reduction in the rate of recurrent sPTD with the administration of probiotics including Clostridium spp., which induce regulatory T cells that play an important role in maintaining pregnancy. The objective of this trial is to evaluate the preventative effects of available oral probiotics, including Clostridium butyricum, on recurrent sPTD. This is a prospective, single-arm, nonblinded, multicenter trial in Japan. The sample size required for this trial is 345 pregnant women with a history of sPTD, considering a clinically significant reduction in the relative risk of 30% (risk ratio=0.7). The primary endpoint is the rate of recurrent sPTD at <37 weeks of gestation. The secondary endpoints are the rate of sPTD at <34 weeks of gestation, the rate of recurrent sPTD at <28 weeks of gestation, the ratio of intestinal Clostridium spp. (detected by next-generation sequencing), and bacterial vaginosis (using the Nugent score). The trial procedures were approved by the Clinical Research Review Board of Toyama University Hospital (SCR2020008) on March 31, 2021. The trial was registered on the Japan Registry of Clinical Trial website on April 28, 2021. Recruitment began on May 1, 2021, and the trial is estimated to finish on March 31, 2025. The findings will clarify the rate of recurrent sPTD following probiotic administration including Clostridium butyricum. Outcomes from this trial will inform clinical practice and guide future randomized controlled trials. Japan Registry of Clinical Trials jRCTs041210014; https://jrct.niph.go.jp/latest-detail/jRCTs041210014. DERR1-10.2196/59928.

O92 EFFICACY AND SAFETY OF LOW-DOSE ANTIHYPERTENSIVE COMBINATION DRUGS INCLUDING AMLODIPINE, TELMISARTAN, AND CHLORTHALIDONE: A MULTICENTER, RANDOMIZED, DOUBLE-BLINDED, PARALLEL, PHASE II CLINICAL TRIAL

Background and Objective: Although single pill high-dose triple antihypertensive combinations are already available on South Korea, there are no reports evaluating the efficacy and safety of the low-dose combination of amlodipine, telmisartan, and chlorthalidone. The aim of this clinical trial was to assess the efficacy and safety of low-dose combination drug containing telmisartan (20 mg), amlodipine (2.5 mg), and chlorthalidone (6.25 mg). Methods: This study was a randomized, double-blinded, parallel, multicenter, phase II clinical trial. In total, 221 subjects from 21 clinical trial sites in South Korea were randomly assigned to groups 1 (AD-209; telmisartan 20 mg/amlodipine 2.5 mg/chlorthalidone 6.25 mg), 2 (AD-209-1A; telmisartan 20 mg/amlodipine 2.5 mg), 3 (AD-209-1B; amlodipine 2.5 mg/chlorthalidone 6.25 mg), and 4 (AD-209-1C; telmisartan 20 mg/chlorthalidone 6.25 mg) in a 1:1:1:1 ratio, and the treatments lasted 8 weeks. After the initial drug administration, the subjects visited the clinical trial sites at weeks 4 and 8 to evaluate drug efficacy and safety. Results: In patients with mild-moderate hypertension, the mean change in MSSBP from baseline to week 8 between group 1 and groups 2, 3, and 4 was -5.93, -8.69, and -1.51 mmHg, respectively. The blood pressure of the subjects in group 1 was significantly lower than that of those in groups 2 and 3. It was also lower than that of subjects in group 4 although this difference was not significant. Among the 221 subjects enrolled, 20 (9.05%) experienced 25 treatment-emergent adverse events (TEAEs); of these, 14 (6.33%) experienced 17 adverse drug reactions (ADRs). No significant differences in the TEAE or ADR incidence rates were found between group 1 and groups 2, 3, and 4. Conclusions: AD-209 (telmisartan 20 mg/amlodipine 2.5 mg/chlorthalidone 6.25 mg), a low-dose triple combination drug, demonstrated a higher blood pressure lowering effect than the corresponding a low-dose dual combination drugs in patients with essential hypertension. Its safety was similar to that of the dual-combination drugs.

Consumption of a Sourdough-Leavened Croissant Enriched with a Blend of Fibers Influences Fasting Blood Glucose in a Randomized Controlled Trial in Healthy Subjects

BackgroundAn incorrect lifestyle, including diet, is responsible for the worldwide dramatic increase in obesity and type 2 diabetes. Increasing dietary fiber consumption may lead to health benefits, and reformulation of bakery products may be a strategy to globally improve the diet. ObjectivesThis study aimed to assess the impact of a 2-wk breakfast consumption with a sourdough-leavened croissant containing a blend of dietary fiber from 10 sources (4.8 g/100 g, croissant enriched with dietary fibers [FIBCRO]), compared with a control croissant (dietary fibers 1.3 g/100 g, CONCRO) on daily energy intake, appetite, metabolic variables, and the gut microbiome. MethodsThirty-two healthy participants were randomly allocated to 2 groups consuming FIBCRO or CONCRO. Participants self-recorded their diet and appetite through 7-d weighted food diaries and visual analog scales every day over the 2 wk. At baseline and after the intervention, fasting blood and urine samples, and fecal samples were collected beside blood pressure, anthropometry, and body composition. Serum glucose, lipids, C-reactive protein, and insulin according to the official methods and serum dipeptidyl peptidase-4 (DPPIV) activity by photometric method were measured. Polyphenols and urolithins in urines were analyzed by Liquid chromatography–tandem mass spectrometry (LC/MS/MS), whereas gut microbiome in feces by shotgun metagenomics. ResultsFIBCRO consumption improved fasting blood glucose compared with CONCRO (mean changes from baseline −2.0 mg/dL in FIBCRO compared with +3.1 mg/dL in CONCRO, P = 0.022), also reducing serum DPPIV activity by 1.7 IU/L (P = 0.01) and increasing urinary excretion of urolithin A-sulfate by 6.9 ng/mg creatinine (P = 0.04) compared with baseline. No further changes in any of the monitored variables or in the gut microbiome were detected. ConclusionsResults suggested that a 2-wk consumption of a sourdough croissant claimed as “source of dietary fiber” improved fasting glycemia compared with a conventional sourdough croissant in healthy subjects. The reduced serum DPPIV activity and increased bioavailability of urolithin likely contributed to determine that effect independently from gut microbiome changes.This trial was registered at clinicaltrials.gov as NCT04999280.

Resource management and capacity planning for clinical trial sites

Background: Since 2020, the number of registered clinical trials has surged by over 30%, significantly increasing the demand for skilled coordinators. Despite this growth, a national shortage of qualified coordinators remains, driven by escalating responsibilities and workloads. Effective resource management is crucial for retention. While the Ontario Protocol Assessment Level (OPAL) helps quantify trial complexity, it overlooks key factors such as organizational structure and budget constraints that impact coordinator productivity. This project aims to refine the OPAL score by integrating it with longitudinal coordinator effort data, improving resource allocation, operational efficiency, and job satisfaction, thereby reducing burnout and turnover. Aim: The aim of this study was to reduce burnout and turnover, ultimately contributing to the overall success of clinical trials.Methods: Actively enrolling interventional studies with corresponding coordinator effort tracking from June 1, 2022, to December 1, 2022, were included in the database. Protocols were graded using an adapted protocol assessment tool. Descriptive statistics compared protocol characteristics to the adapted assessment score and tracked coordinator hours, while Student’s t-test and univariate analysis evaluated differences in continuous variables. Linear regression analysis assessed the association between the adapted score and the coordinator effort. Results: Seven protocols were analyzed: five (71%) were federally funded, two (29%) were industry-sponsored; four (57%) were behavioral interventions, and three (43%) were drug studies. Significant differences were observed between industry-sponsored and federally funded studies (7.25 ± 1.77 vs. 6.45 ± 1.65; P &lt; 0.0001) and between behavioral interventions and drug studies (6.88 ± 1.56 vs. 6.42 ± 1.91; P &lt; 0.0001). Linear regression revealed the adapted OPAL score significantly predicted coordinator hours (β = 77.22; P = 0.01; R2 = 0.78). Conclusion: The adapted protocol complexity scores predict coordinator effort, aiding in capacity assessment and objective project distribution. Relevance for Patients: The findings from this project can inform more precise resource allocation, potentially leading to higher-quality studies and enhanced participant safety.

The effect of using the hip exoskeleton assistive (HEXA) robot compared to conventional physiotherapy on clinical functional outcomes in stroke patients with hemiplegia: a pilot randomized controlled trial

Trial designThis study is a pilot randomized clinical trial aimed to investigate the effect of using Hip Exoskeleton Assistive (HEXA) robot compared to conventional physiotherapy on the quality of walking, disability, and quality of life of stroke patients with hemiplegia.MethodsIn this study, 24 patients were randomly assigned to the intervention group (robotic physiotherapy with HEXA robot), or control group (conventional physiotherapy). In each session, both groups received 30 min of conventional physiotherapy including electrotherapy and conventional exercises, and then the intervention group did gait training for 30 min with the HEXA robot and the control group for 30 min without the HEXA robot. The treatment program was 12 sessions, 3 times a week. Before the 1st and after the 12th sessions, both groups were evaluated for walking quality, disability, and quality of life.ResultsThe results showed that the main effect of time was significant (P < 0.05) in all outcomes and patients in both groups achieved significant improvement in all outcomes after the intervention. The main effect of the group was also significant in the outcomes of 6MWT (P < 0.05) and TUG (P < 0.05), and the intervention group patients experienced more distance and speed in these two tests. This study was approved by the ethics committee of Mashhad University of Medical Sciences (IR.MUMS.FHMPM.REC.1400.079 dated 28th Jan 2022). The trial was registered with the clinical trials site of www.IRCT.ir (IRCT20210730052024N1) on January 28th 2022.ConclusionIt seems that the HEXA robot can effectively improve walking capacity and speed.