INSTRuCT: Protocol, Infrastructure, and Governance

Stroke ◽  
2021 ◽  
Author(s):  
Jeyaraj Durai Pandian ◽  
Shweta Jain Verma ◽  
Deepti Arora ◽  
Meenakshi Sharma ◽  
Rupinder Dhaliwal ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Medical Research ◽  
Large Scale ◽  
Second Phase ◽  
Indian Council ◽  
Trial Network ◽  
Clinical Trial Network

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/ ; Unique Identifier: CTRI/2017/05/008507.

scholarly journals Clinical Trials Evaluating Proton Therapy

2021 ◽  
Author(s):  
Paige A. Taylor
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Proton Therapy ◽  
Clinical Implementation ◽  
Cancer Disease ◽  
International Networks ◽  
The Past ◽  
Trial Network ◽  
Clinical Trial Network

Although proton therapy was developed almost 80 years ago, widespread clinical implementation has been limited until the past decade. With the growing use of proton therapy, there is a desire to prove the equivalence or superiority of proton therapy across a number of cancer disease sites. Dozens of clinical trials have been developed to accomplish this within individual institutions, among a few centers, and across national and international networks such as the National Cancer Institute’s National Clinical Trial Network. The protocols include proton therapy imbedded in trials with photon therapy as well as randomized photon vs. proton trials. This chapter provides an overview of the design of such trials as well as some of the challenges facing protocols with proton therapy.

scholarly journals SO093LONGITUDINAL DATA ON TREATMENT DURATION AND COMPLIANCE FROM AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE CLINICAL TRIALS WITH TOLVAPTAN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Xiaolei Zhou ◽  
Diana Garbinsky ◽  
John Ouyang ◽  
Eric Davenport ◽  
Indra Agarwal ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Treatment Duration ◽  
Treatment Time ◽  
Treatment Compliance ◽  
Kidney Volume ◽  
Total Kidney Volume ◽  
Treatment Gaps ◽  
Clinical Trial Program

Abstract Background and Aims : Observation of impactful clinical outcomes in a clinical trial setting for ADPKD is challenging due to the life-long progressive nature of ADPKD and longer-term associated outcomes of interest in this population (e.g., renal function decline, cardiovascular events, and mortality). Since 2004, the tolvaptan (TOL) clinical trial program enrolled subjects in multiple clinical studies with the opportunity to enroll in subsequent clinical trials for treatment and outcomes evaluation. Method : Data from 6 ADPKD studies (protocols 156-04-250, 156-04-251, 156-06-260, 156-09-284, 156-09-290, 156-08-271) were pooled and evaluated over time for overall treatment duration, treatment time, and treatment gaps. Treatment duration for the individual clinical trials ranged from 1 week to up to 3 years. Results : Overall, 1,437 subjects received TOL in these ADPKD clinical trials. For these subjects, the mean overall treatment duration was 4.1 years (3.8 years on treatment) with a maximum of 9.7 years (9.0 years on treatment). In this cohort, 513 subjects (35.7%) received TOL treatment for more than 5 years. Mean treatment compliance was 94.1%. Overall, 723 subjects (50.3%) received TOL treatment in ≥2 trials, with a median treatment gap duration between trials of 0.1 years (maximum, 5.6 years). At least 7 years of follow-up data are available for estimated glomerular filtration rate in 241 subjects (mean at baseline, 78.6 mL/min/1.73m2) and for total kidney volume in 130 subjects (mean at baseline, 1,816.9 mL). Conclusion : This analysis provides longitudinal follow-up over an extended timeframe in a large number of subjects treated with TOL, with the greatest number of subjects being enrolled in clinical trials enriched for rapidly progressing ADPKD. Treatment compliance over years was reasonably good despite treatment gaps.

scholarly journals Oversight and management of a cell therapy clinical trial network: Experience and lessons learned

2011 ◽  
Vol 32 (5) ◽  
pp. 614-619 ◽  
Author(s):  
Lemuel A. Moyé ◽  
Shelly L. Sayre ◽  
Lynette Westbrook ◽  
Beth C. Jorgenson ◽  
Eileen Handberg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Therapy ◽  
Lessons Learned ◽  
Trial Network ◽  
Clinical Trial Network ◽  
A Cell ◽  
Therapy Clinical Trial

Abstract TP138: Repeated Bilateral Multifocal Cortical Magnetic Stimulation with a New Wearable Transcranial Stimulator in Chronic Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Santosh Helekar ◽  
Blessy John ◽  
Rafferty Laredo ◽  
Cynthia Card ◽  
Charles McCane ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Ischemic Stroke ◽  
Grip Strength ◽  
Pulse Duration ◽  
Motor Function ◽  
Gait Speed ◽  
Magnetic Stimulation ◽  
Cortical Reorganization ◽  
In Cis

Introduction: Repetitive transcranial magnetic stimulation (rTMS) treatment of ipsilesional (IL) or contralesional (CL) cortex combined with occupational/physical therapy (OT/PT) shows significant promise in chronic ischemic stroke (CIS). Here we describe a multifocal cortical magnetic stimulation protocol with a new wearable device called transcranial rotating permanent magnet stimulator (TRPMS) for a pilot clinical trial in CIS, and present preliminary results in one patient. Hypothesis: Simultaneous repeated excitatory and inhibitory stimulations of IL and CL cortical sites, respectively cause perilesional functional cortical reorganization with recovery of motor function in CIS. Methods: After informed consent, we treated a 58-year old male patient with a right middle cerebral artery thromboembolic infarct causing left sided hemiparesis. At the start of TRPMS treatment 19 months after the stroke he had a stable baseline on motor function tests. The treatment consisted of 4 two-week sessions (with intervening one-week rest periods) of daily (on week days) 40 min TRPMS stimulation (5 Hz, 25 ms pulse duration at 4 perilesional cortical sites, and 0.2 Hz, 100 ms pulse duration at 2 CL primary motor cortical sites) accompanied by OT/PT. Pretreatment, posttreatment and follow-up assessments were functional magnetic resonance imaging (fMRI) during attempted gripping movements, and grip strength, gait speed and Fugl-Meyer (FM) scale testing. Results: After the 2 nd treatment session movement-related fMRI showed increasing levels of neural activation of the stimulated intact cortex surrounding the lesion. Grip strength of the affected hand increased ~2.5 fold. Gait speed increased by ~15%. Left lower extremity motor function and sensation measures on the FM scale showed sustained increase by ~17% and ~30%, respectively. These changes persisted above the pretreatment levels at the 3-month follow-up. There were no adverse effects. Conclusions: These findings suggest that the new TRPMS protocol might bring about some degree of functional cortical reorganization and motor recovery in CIS. We have therefore launched a randomized double-blind sham treatment-controlled clinical trial involving a four-week TRPMS treatment in 30 CIS patients.

Dedicated clinical trial tissue tracking database to improve turn-around time at high-volume center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1543-1543
Author(s):  
Peter Blankenship ◽  
David DeLaRosa ◽  
Marc Burris ◽  
Steven Cusson ◽  
Kayla Hendricks ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tissue Sample ◽  
High Volume ◽  
Trial Participation ◽  
Fresh Tissue ◽  
Oncology Clinical Trials ◽  
The Status ◽  
Unique Source

1543 Background: Tissue requirements in oncology clinical trials are increasingly complex due to prescreening protocols for patient selection and serial biopsies to understand molecular-level treatment effects. Novel solutions for tissue processing are necessary for timely tissue procurement. Based on these needs, we developed a Tissue Tracker (TT), a comprehensive database for study-related tissue tasks at our high-volume clinical trial center. Methods: In this Microsoft Access database, patients are assigned an ID within the TT that is associated with their name, medical record number, and study that follows their request to external users: pathology departments, clinical trial coordinators and data team members. To complete tasks in the TT, relevant information is required to update the status. Due to the high number of archival tissue requests from unique pathology labs, the TT has a “Follow-Up Dashboard” that organizes information needed to conduct follow-up on all archival samples with the status “Requested”. This results in an autogenerated email and pdf report sent to necessary teams. The TT also includes a kit inventory system and a real-time read only version formatted for interdepartmental communication, metric reporting, and other data-driven efforts. The primary outcome in this study was to evaluate our average turnaround time (ATAT: average time from request to shipment) for archival and fresh tissue samples before and after TT development. Results: Before implementing the TT, between March 2016 and March 2018, we processed 2676 archival requests from 235 unique source labs resulting in 2040 shipments with an ATAT of 19.29 days. We also processed 1099 fresh biopsies resulting in 944 shipments with an ATAT of 7.72 days. After TT implementation, between April 2018 and April 2020, we processed 2664 archival requests from 204 unique source labs resulting in 2506 shipments (+28.0%) with an ATAT of 14.78 days (-23.4%). During that same period, we processed 1795 fresh biopsies (+63.3%) resulting in 2006 shipments (+112.5%) with an ATAT of 6.85 days (-11.3%). Conclusions: Oncology clinical trials continue to evolve toward more extensive tissue requirements for prescreening and scientific exploration of on-treatment molecular profiling. Timely results are required to optimize patient trial participation. During the intervention period, our tissue sample volume and shipments increased, but the development and implementation of an automated tracking system allowed improvement in ATAT of both archival and fresh tissue. This automation not only improves end-user expectations and experiences for patients and trial sponsors but this allows our team to adapt to the increasing interest in tissue exploration.

scholarly journals Results availability and timeliness of registered COVID-19 clinical trials: interim cross-sectional results from the DIRECCT study

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e053096
Author(s):  
Maia Salholz-Hillel ◽  
Peter Grabitz ◽  
Molly Pugh-Jones ◽  
Daniel Strech ◽  
Nicholas J DeVito
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Journal Article ◽  
Cross Sectional Study ◽  
Sensitivity Analyses ◽  
Cross Sectional ◽  
Registration Data ◽  
Clinical Trial Registries ◽  
Treatment And Prevention

ObjectiveTo examine how and when the results of COVID-19 clinical trials are disseminated.DesignCross-sectional study.SettingThe COVID-19 clinical trial landscape.Participants285 registered interventional clinical trials for the treatment and prevention of COVID-19 completed by 30 June 2020.Main outcome measuresOverall reporting and reporting by dissemination route (ie, by journal article, preprint or results on a registry); time to reporting by dissemination route.ResultsFollowing automated and manual searches of the COVID-19 literature, we located 41 trials (14%) with results spread across 47 individual results publications published by 15 August 2020. The most common dissemination route was preprints (n=25) followed by journal articles (n=18), and results on a registry (n=2). Of these, four trials were available as both a preprint and journal publication. The cumulative incidence of any reporting surpassed 20% at 119 days from completion. Sensitivity analyses using alternate dates and definitions of results did not appreciably change the reporting percentage. Expanding minimum follow-up time to 3 months increased the overall reporting percentage to 19%.ConclusionCOVID-19 trials completed during the first 6 months of the pandemic did not consistently yield rapid results in the literature or on clinical trial registries. Our findings suggest that the COVID-19 response may be seeing quicker results disclosure compared with non-emergency conditions. Issues with the reliability and timeliness of trial registration data may impact our estimates. Ensuring registry data are accurate should be a priority for the research community during a pandemic. Data collection is underway for the next phase of the DIssemination of REgistered COVID-19 Clinical Trials study expanding both our trial population and follow-up time.

scholarly journals Large-scale phenome-wide association study of PCSK9 loss-of-function variants demonstrates protection against ischemic stroke

2017 ◽  
Author(s):  
Abhiram S. Rao ◽  
Daniel Lindholm ◽  
Manuel A. Rivas ◽  
Joshua W. Knowles ◽  
Stephen B. Montgomery ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ischemic Stroke ◽  
Protective Effect ◽  
Large Scale ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Genetic Associations ◽  
Loss Of Function

AbstractPCSK9 inhibitors are a potent new therapy for hypercholesterolemia and have been shown to decrease risk of coronary heart disease. Although short-term clinical trial results have not demonstrated major adverse effects, long-term data will not be available for some time. Genetic studies in large well-phenotyped biobanks offer a unique opportunity to predict drug effects and provide context for the evaluation of future clinical trial outcomes. We tested association of the PCSK9 loss-of-function variant rsll591147 (R46L) in a hypothesis-driven 11 phenotype set and a hypothesis-generating 278 phenotype set in 337,536 individuals of British ancestry in the United Kingdom Biobank (UKB), with independent discovery (n = 225K) and replication (n = 112K). In addition to the known association with lipid levels (OR 0.63) and coronary heart disease (OR 0.73), the T allele of rs11591147 showed a protective effect on ischemic stroke (OR 0.61, p = 0.002) but not hemorrhagic stroke in the hypothesis-driven screen. We did not observe an association with type 2 diabetes, cataracts, heart failure, atrial fibrillation, and cognitive dysfunction. In the phenome-wide screen, the variant was associated with a reduction in metabolic disorders, ischemic heart disease, coronary artery bypass graft operations, percutaneous coronary interventions and history of angina. A single variant analysis of UKB data using TreeWAS, a Bayesian analysis framework to study genetic associations leveraging phenotype correlations, also showed evidence of association with cerebral infarction and vascular occlusion. This result represents the first genetic evidence in a large cohort for the protective effect of PCSK9 inhibition on ischemic stroke, and corroborates exploratory evidence from clinical trials. PCSK9 inhibition was not associated with variables other than those related to low density lipoprotein cholesterol and atherosclerosis, suggesting that other effects are either small or absent.

482Direct oral anticoagulant rivaroxaban in very old and frail patients: A one-year prospective follow-up of a large-scale cohort (SAFIR-AC)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Hanon ◽  
J Vidal ◽  
E Chaussade ◽  
J P David ◽  
N Boulloche ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Major Bleeding ◽  
Large Scale ◽  
Bleeding Risk ◽  
Geriatric Population ◽  
Very Old ◽  
The Mean ◽  
One Year ◽  
The One

Abstract Background/Introduction Age is one of the strongest predictors/risk factors for ischemic stroke in subjects with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) have been shown to be effective in the prevention of this condition; however, clinical evidence on bleeding risk with this therapeutic strategy in very old and frail geriatric patients is poor. Purpose To assess bleeding risk in French geriatric patients aged ≥80 years and diagnosed with AF newly treated with rivaroxaban. Methods Subjects, presenting to one of 33 geriatric centers, with non-valvular AF and recent initiation of a treatment with rivaroxaban were enrolled in the study and followed-up every 3 months for 12 months. Clinical and routine laboratory data and evaluation scores, such as HAS-BLED, HEMORR2HAGES, ATRIA, and CHA2DS2-VASc, as well as comprehensive geriatric evaluation were reported. Major bleeding, as defined in ROCKET AF study, was reported at each visit, and this primary outcome was adjudicated by an independent committee. Results of this cohort were compared with findings from a similar cohort treated with vitamin K antagonists (VKAs) from the same centers (n=924). Results A total of 1045 subjects were enrolled in the study of whom 995 (95%) had a one-year follow-up (analyzed population). The mean (standard deviation (SD)) age was 86.0 (4.3) years, with the majority of patients being female (61%), 23% aged 90 years or older, and 48% having an estimated glomerular filtration rate (eGFR) <50 mL/min. The main comorbidities were hypertension in 77% of subjects, malnutrition 49%, anemia 43%, dementia 39%, heart failure 36%, and falls 27%. The mean (SD) score for CHA2DS2-VASc was 4.8 (1.4), HAS-BLED 2.4 (0.9), Mini-Mental State Examination (MMSE) 21.5 (6.9), Activities of Daily Living (ADL) 4.4 (1.9), and Charlson Comorbidity Index 6.7 (2.0). The one-year rate of major bleeding events was 6.4% of which 0.8% were fatal and 1.1% intracranial hemorrhages (ICH), whereas the one-year rate of ischemic stroke was 1.4% and all-cause mortality 17.9%. Computed with VKA cohort findings and adjusted for age, gender, eGFR and Charlson score, this would result in a hazard ratio of 0.54 (95% confidence interval [CI], 0.38 to 0.78) for major bleeding, 0.36 (0.17 to 0.76) for ICH, 0.62 (0.29 to 1.33) for ischemic stroke, and 0.82 (0.65 to 1.02) for all-cause mortality, in favor of rivaroxaban. Conclusions This is the first large-scale prospective study in geriatric population in AF subjects treated with DOAC (rivaroxaban) Major bleeding risk appeared higher in very old than younger population, however major bleeding and ICH rates were significantly lower with rivaroxaban than with VKAs when used in the same geriatric population. This study indicates that Rivaroxaban can be used in very old and frail patients for the treatment of non-valvular AF. Acknowledgement/Funding Unrestricted grant from Bayer

scholarly journals Patients with cancer in the COVID-19 era: the clinical trial issue

2020 ◽  
Vol 106 (4) ◽  
pp. 271-272 ◽  
Author(s):  
Marcello Scarcia ◽  
Giuseppe Mario Ludovico ◽  
Angela Fortunato ◽  
Alba Fiorentino
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Physical Examination ◽  
Regulatory Agencies ◽  
Study Medication ◽  
Therapeutic Modalities ◽  
Patients With Cancer ◽  
Safety Guidelines ◽  
Trial Discontinuation

Coronavirus disease 2019 (COVID-19) hospital reorganization may result in reduced ability for the hospital to fully use its armamentarium for battling cancer. Thus different therapeutic modalities have been recommended. During the pandemic, despite regulatory agencies’ recommendations, several considerations and doubts remain for oncologic clinical trials. Considering patients who had been enrolled before the pandemic, and who plan to take the study medication, the situation becomes complicated. These patients should undergo monitoring visits, blood sampling, questionnaire, physical examination, and drug and radiation administration. To avoid deviations from the protocol and trial discontinuation, follow-up should be performed regularly, in concordance with safety guidelines. Here we report several considerations.

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