National Institutes of Health StrokeNet During the Time of COVID-19 and Beyond
2020; Lippincott Williams & Wilkins; Volume: 51; Issue: 8 Linguagem: Inglês
10.1161/strokeaha.120.030417
ISSN1524-4628
AutoresJoseph P. Broderick, Jordan Elm, L. Scott Janis, Wenle Zhao, Claudia S. Moy, Catherine Dillon, Marc I. Chimowitz, Ralph L. Sacco, Steven C. Cramer, Steven L. Wolf, Karen C. Johnston, Jeffrey L. Saver, Randolph S. Marshall, D. A. Brown, Max Wintermark, Mitchell S.V. Elkind, Hooman Kamel, David Tirschwell, W.T. Longstreth, Ronald D. Chervin, Opeolu Adeoye, Andrew D. Barreto, James C. Grotta, Sharon Landesman Ramey, Warren Lo, Wuwei Feng, Gottfried Schlaug, Kevin N. Sheth, Magdy Selim, Andrew M. Naidech, Maarten G. Lansberg, Ronald M. Lazar, Gregory W. Albers, Jessica Griffin, Logan P. Sirline, Jamey Frasure, Clinton B. Wright, Pooja Khatri,
Tópico(s)Venous Thromboembolism Diagnosis and Management
ResumoHomeStrokeVol. 51, No. 8National Institutes of Health StrokeNet During the Time of COVID-19 and Beyond Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBNational Institutes of Health StrokeNet During the Time of COVID-19 and Beyond Joseph P. Broderick, Jordan J. Elm, L. Scott Janis, Wenle Zhao, Claudia S. Moy, Catherine R. Dillon, Marc I. Chimowitz, Ralph L. Sacco, Steven C. Cramer, Steven L. Wolf, Karen C. Johnston, Jeffrey L. Saver, Randolph S. Marshall, Devin Brown, Max Wintermark, Mitchell S.V. Elkind, Hooman Kamel, David L. Tirschwell, W.T. Longstreth, Ronald D. Chervin, Opeolu M. Adeoye, Andrew D. Barreto, James C. Grotta, Sharon L. Ramey, Warren D. Lo, Wuwei Feng, Gottfried Schlaug, Kevin N. Sheth, Magdy Selim, Andrew M. Naidech, Maarten G. Lansberg, Ronald M. Lazar, Gregory W. Albers, Jessica S. Griffin, Logan P. Sirline, Jamey Frasure, Clinton B. Wright, Pooja Khatri and on behalf of the NIH StrokeNet Investigators Joseph P. BroderickJoseph P. Broderick Correspondence to: Joseph P. Broderick, MD, Department of Neurology and Rehabilitation Medicine, University of Cincinnati Gardner Neuroscience Institute, 260 Stetson St, Suite 2300, PO Box 670525, Cincinnati, OH. Email: E-mail Address: [email protected] https://orcid.org/0000-0002-7323-7709 Departments of Neurology and Rehabilitation Medicine (J.P.B., P.K., J.F., O.M.A.), University of Cincinnati Neuroscience Institute, University of Cincinnati Academic Health Center, OH. Emergency Medicine (J.P.B., P.K., J.F., O.M.A.), University of Cincinnati Neuroscience Institute, University of Cincinnati Academic Health Center, OH. , Jordan J. ElmJordan J. Elm Public Health Sciences (J.J.E., W.Z., C.R.D., J.S.G., L.P.S.), Medical University of South Carolina, Charleston. , L. Scott JanisL. Scott Janis National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (L.S.J., C.S.M., C.B.W.). , Wenle ZhaoWenle Zhao Public Health Sciences (J.J.E., W.Z., C.R.D., J.S.G., L.P.S.), Medical University of South Carolina, Charleston. , Claudia S. MoyClaudia S. Moy National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (L.S.J., C.S.M., C.B.W.). , Catherine R. DillonCatherine R. Dillon Public Health Sciences (J.J.E., W.Z., C.R.D., J.S.G., L.P.S.), Medical University of South Carolina, Charleston. , Marc I. ChimowitzMarc I. Chimowitz Departments of Neurology (M.I.C.), Medical University of South Carolina, Charleston. , Ralph L. SaccoRalph L. Sacco Department of Neurology, Miller School of Medicine, University of Miami, FL (R.L.S.). , Steven C. CramerSteven C. Cramer UCLA Department of Neurology, California Rehabilitation Institute, Los Angeles (S.C.C., J.L.S.). , Steven L. WolfSteven L. Wolf Department of Rehabilitation Medicine, Division of Physical Therapy, Emory University School of Medicine, Atlanta, GA (S.L.W.). , Karen C. JohnstonKaren C. Johnston Department of Neurology, University of Virginia, Charlottesville (K.C.J.). , Jeffrey L. SaverJeffrey L. Saver UCLA Department of Neurology, California Rehabilitation Institute, Los Angeles (S.C.C., J.L.S.). , Randolph S. MarshallRandolph S. Marshall Department of Neurology, Vagelos College of Physicians and Surgeons (R.S.M., M.S.V.E), Columbia University, New York, NY. , Devin BrownDevin Brown Department of Neurology, Michigan Medicine, Ann Arbor (D.B., R.D.C.). , Max WintermarkMax Wintermark Department of Rehabilitation Medicine, Division of Physical Therapy, Emory University School of Medicine, Atlanta, GA (S.L.W.). , Mitchell S.V. ElkindMitchell S.V. Elkind Department of Neurology, Vagelos College of Physicians and Surgeons (R.S.M., M.S.V.E), Columbia University, New York, NY. Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY. , Hooman KamelHooman Kamel , David L. TirschwellDavid L. Tirschwell Department of Neurology, School of Medicine (W.T.L., D.L.T.), University of Washington, Seattle. , W.T. LongstrethW.T. Longstreth Department of Neurology, School of Medicine (W.T.L., D.L.T.), University of Washington, Seattle. Department of Epidemiology, School of Public Health (W.T.L.), University of Washington, Seattle. , Ronald D. ChervinRonald D. Chervin Department of Neurology, Michigan Medicine, Ann Arbor (D.B., R.D.C.). , Opeolu M. AdeoyeOpeolu M. Adeoye Departments of Neurology and Rehabilitation Medicine (J.P.B., P.K., J.F., O.M.A.), University of Cincinnati Neuroscience Institute, University of Cincinnati Academic Health Center, OH. Emergency Medicine (J.P.B., P.K., J.F., O.M.A.), University of Cincinnati Neuroscience Institute, University of Cincinnati Academic Health Center, OH. , Andrew D. BarretoAndrew D. Barreto Department of Neurology, Stroke Program, McGovern Medical School at The University of Texas Health Science Center at Houston (A.D.B.). , James C. GrottaJames C. Grotta Memorial Hermann Hospital-Texas Medical Center (J.C.G.). , Sharon L. RameySharon L. Ramey Departments of Psychiatry and Behavioral Medicine (S.L.R.), Fralin Biomedical Research Institute, Virginia Tech, Roanoke. Psychology (S.L.R.), Fralin Biomedical Research Institute, Virginia Tech, Roanoke. Neuroscience (S.L.R.), Fralin Biomedical Research Institute, Virginia Tech, Roanoke. Human Development (S.L.R.), Fralin Biomedical Research Institute, Virginia Tech, Roanoke. , Warren D. LoWarren D. Lo Departments of Pediatrics (W.D.L.), Ohio State University and Nationwide Children's Hospital, Columbus. Neurology (W.D.L.), Ohio State University and Nationwide Children's Hospital, Columbus. , Wuwei FengWuwei Feng Department of Neurology, Duke University Medical Center, Durham, NC (W.F.). , Gottfried SchlaugGottfried Schlaug Brain Repair and NeuroRestoration Center, Baystate Medical Center, University of Massachusetts Medical School and Institute of Applied Life Sciences–UMass Amherst, Springfield-Amherst (G.S.). , Kevin N. ShethKevin N. Sheth Department of Neurology, Yale School of Medicine and Yale New Haven Hospital, CT (K.N.S.). , Magdy SelimMagdy Selim Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA (M.S.). , Andrew M. NaidechAndrew M. Naidech Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL (A.M.N.). , Maarten G. LansbergMaarten G. Lansberg Departments of Neurology and Neurological Sciences (G.W.A., M.G.L.) Stanford University School of Medicine, CA. , Ronald M. LazarRonald M. Lazar Department of Neurology, University of Alabama at Birmingham (R.M.L.). , Gregory W. AlbersGregory W. Albers Departments of Neurology and Neurological Sciences (G.W.A., M.G.L.) Stanford University School of Medicine, CA. , Jessica S. GriffinJessica S. Griffin Public Health Sciences (J.J.E., W.Z., C.R.D., J.S.G., L.P.S.), Medical University of South Carolina, Charleston. , Logan P. SirlineLogan P. Sirline Public Health Sciences (J.J.E., W.Z., C.R.D., J.S.G., L.P.S.), Medical University of South Carolina, Charleston. , Jamey FrasureJamey Frasure Departments of Neurology and Rehabilitation Medicine (J.P.B., P.K., J.F., O.M.A.), University of Cincinnati Neuroscience Institute, University of Cincinnati Academic Health Center, OH. Emergency Medicine (J.P.B., P.K., J.F., O.M.A.), University of Cincinnati Neuroscience Institute, University of Cincinnati Academic Health Center, OH. , Clinton B. WrightClinton B. Wright National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (L.S.J., C.S.M., C.B.W.). , Pooja KhatriPooja Khatri Departments of Neurology and Rehabilitation Medicine (J.P.B., P.K., J.F., O.M.A.), University of Cincinnati Neuroscience Institute, University of Cincinnati Academic Health Center, OH. Emergency Medicine (J.P.B., P.K., J.F., O.M.A.), University of Cincinnati Neuroscience Institute, University of Cincinnati Academic Health Center, OH. and on behalf of the NIH StrokeNet Investigators Originally published24 Jun 2020https://doi.org/10.1161/STROKEAHA.120.030417Stroke. 2020;51:2580–2586Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 24, 2020: Ahead of Print The National Institute of Neurological Disorders and Stroke (NINDS) established the National Institutes of Health (NIH) StrokeNet in the fall of 2013 to facilitate the rapid initiation and efficient implementation of small and large multisite exploratory and confirmatory clinical trials of stroke prevention, treatment, and recovery, as well as validation studies of biomarkers or outcome measures. NIH StrokeNet sprang from an earlier NINDS-funded clinical trial network called Specialized Programs of Translational Research in Acute Stroke that focused only on phase II clinical trials and biomarker studies of acute stroke. Since the publication of the NIH StrokeNet User Guide in 2016 that detailed the organizational structure, as well as the development and implementation of trials within the network,1 NIH StrokeNet has grown substantially in the number of participating clinical sites, the number of ongoing trials, and scientific and educational impact. We provide a summary of the first 7 years of the network, the completed and ongoing trials, the recent impact of coronavirus disease 2019 (COVID-19) on the network, and a blueprint for reinstitution of clinical trial enrollment following the COVID-19 pandemic. Detailed information regarding the NIH StrokeNet, its ongoing trials, and educational webinars can be found at the website https://www.nihstrokenet.org/.Evolution of StrokeNet and StrokeNet TrialsThe initial task of the first years of StrokeNet was development of the network infrastructure including the National Coordinating Center; National Data Management and Statistical Center; 25 participating regional coordinating centers, sites within each regional network; a central institutional review board for all participating clinical research sites; a central research pharmacy; prevention, acute stroke, and recovery working groups; education and imaging cores; key committees; and the NIH StrokeNet Data and Safety Monitoring Board. The network has grown dramatically with 27 regional coordinating centers and over 500 clinical research sites throughout the United States.While the infrastructure was under development, StrokeNet also solicited, developed, and submitted clinical trial proposals for potential funding. Investigators refine concept proposals as they deem fit and submit to the NINDS to determine alignment with programmatic priorities. If NINDS approves concept proposals, investigators return to the network for assessment of feasibility through both detailed surveys of StrokeNet sites and a population-based epidemiological assessment, before the final trial submission to the NIH for peer review. Since the process began, 109 unique concept proposals have been submitted of which 37 were submitted to NIH for formal review by NIH Study Section (3 are currently pending review). Of these, NINDS has funded 10.The NINDS designed the NIH StrokeNet to support phase II and phase III stroke trials. During the first years of the network, NIH StrokeNet focused on developing infrastructure and new proposals and assisting in the completion of trials already funded by NINDS. These previously funded trials included the following trials completed with NIH StrokeNet assistance: the NETT (Neurology Emergencies Treatment Trial) Network supported POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke)2 and SHINE trials (Stroke Hyperglycemia Insulin Network Effort),3 the NeuroNEXT (Network for Excellence in Neuroscience Clinical Trials) supported RHAPSODY trial (Safety Evaluation of 3K3A-APC in Ischemic Stroke),4 and the MISTIE 3 (Minimally Invasive Surgery Plus r-tPA for ICH Evacuation)5 and i-DEF trials (Intracerebral Hemorrhage Deferoxamine).6 Additionally, the NIH StrokeNet continues to assist 2 ongoing studies funded before initiation of the network: CREST 2 (Carotid Revascularization Endarterectomy vs Stenting)7 and CREST H.8 The first 3 trials implemented fully by StrokeNet were DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3),9 Telerehab,10 and ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke).11 For DEFUSE 3 and ARCADIA, the design, funding, and implementation occurred entirely within StrokeNet. Telerehab was originally designed outside the network framework and approved for funding as a single-center study and then adapted and implemented into StrokeNet after the funding decision.The first of these multicenter trials fully designed within the network, DEFUSE 3 (Table 1),9 was funded in September 2015. This phase 3 randomized trial compared thrombectomy and standard medical therapy versus standard medical therapy alone in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was potentially salvageable. DEFUSE 3 stopped early in the summer of 2017 for overwhelming efficacy. In 2019, the trial received a Distinguished Clinical Research Achievement Award. This award was presented to the top 2 studies among all nominated clinical trials in the United States in 2018, "that show creativity, innovation, or a novel approach which demonstrated an immediate impact on the health and well-being of patients."Table 1. Current Status of StrokeNet Trials (Enrollment Suspended for All Trials Because of COVID-19 on March 24)NIH StrokeNet TrialsPrimary Study QuestionNotice of AwardDate of First EnrollmentPlanned SitesTarget Number of Randomized ParticipantsRandomized ParticipantsARCADIA* phase IIIIs apixaban superior to aspirin for the prevention of recurrent stroke in participants with cryptogenic ischemic stroke and atrial cardiopathy?May 2017March 12, 2018120 (now 180)1100441MOST phase IIIDoes eptifibatide, argatroban, or placebo added to IV tPA, started within 3 h of onset, improve outcome in ischemic stroke subjects at 90 d?June 2018October 15, 2019110120033Sleep SMART* phase IIIDoes treatment of OSA with positive airway pressure starting shortly after acute ischemic stroke or high-risk TIA (1) reduce recurrent stroke, acute coronary syndrome, and all-cause mortality during 6 mo after the event and (2) improve stroke outcomes at 3 mo in patients who experienced an ischemic stroke?August 2018May 31, 2019110 (now 140)3062253TRANSPORT2 phase IIDo 3 dose regimens of noninvasive brain stimulation (including sham stimulation) plus modified constraint-induced movement therapy lead to a differential change in motor impairment in the upper extremity after a 10-session intervention?August 2018September 9, 201912 (now 15)12912I-ACQUIRE phase IIIIn 8- to 36-mo-old children with perinatal arterial stroke, does intensive pediatric rehabilitation at either 3 h/d (moderate dose) or 6 h/d (high dose) for 5 d/wk for 4 wk improve outcome at 7 d after treatment and at 6 mo, as compared with usual and customary treatment?February 2019October 10, 20191224022ARCADIA-CSI* phase III ancillaryDo patients in the ARCADIA trial on apixaban experience less cognitive decline and fewer silent infarcts than those on aspirin therapy?July 2019November 14, 201910050052ASPIRE phase IIIIs apixaban superior to aspirin for prevention of the composite outcome of any stroke (hemorrhagic or ischemic) or death from any cause in patients with recent ICH and atrial fibrillation?July 2019May 26, 20201257001SATURN phase III pragmaticWhether continuation vs discontinuation of statin drugs after spontaneous lobar ICH is the best strategy, and whether the decision to continue/discontinue statins should be influenced by an individual's APOE genotype?September 2019NA14014560FASTEST* phase IIIDoes treatment with rFVIIa within 2 hours of onset in appropriately selected patients with spontaneous ICH improve outcome, as measured by the ordinal distribution of the mRS at 180 d, as compared with placebo?February 2020NA1158600Completed trialsDEFUSE 3* phase IIIIs thrombectomy plus standard medical therapy superior to standard medical therapy alone in improving outcome at 90 d, in patients 6 to 16 h after they were last known to be well and who have remaining ischemic brain tissue that was potentially salvageable?September 2015May 6, 201645476182Telerehab phase IIWhether a 6-wk course of intensive home-based telehealth therapy targeting arm movements after stroke would provide rehabilitation benefits that are comparable with those derived from dose-matched traditional in-clinic rehabilitation therapy?September 18, 20155124124APOE indicates apolipoprotein-E; ARCADIA, Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke; ARCADIA-CSI, Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke–Cognition and Silent Infarcts; ASPIRE, Anticoagulation for Stroke Prevention and Recovery After Intracerebral Hemorrhage; COVID-19, coronavirus disease 2019; DEFUSE, Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3; FASTEST, FVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time; I-ACQUIRE, Infant ACQUIRE; ICH, intracerebral hemorrhage; IV tPA, intravenous tissue-type plasminogen activator; MOST, Multi-Arm Optimization of Stroke Thrombolysis; mRS, modified Rankin Scale; NA, not applicable; NIH, National Institutes of Health; OSA, obstructive sleep apnea; rFVIIa, recombinant factor VIIa; SATURN, Statins Use in Intracerebral Patient; Sleep SMART, Sleep for Stroke Management and Recovery Trial; TIA, transient ischemic attack; and TRANSPORT2, Transcranial Direct Current Stimulation for Post-Stroke Motor Recovery A Phase II Study.*Industry partnership.The second trial, the Telerehabilitation trial, was the first multicenter trial of telerehabilitation versus standard in-person physical therapy.10 The trial demonstrated that 6 weeks of intensive therapy substantially improved function and that telerehabilitation was not inferior to traditional in-clinic rehabilitation for improving motor status (Fugl-Meyer arm motor scale). The trial design was prescient given the social distancing required during the ongoing COVID-19 pandemic and likely represents the digital future of ambulatory physical therapy for certain groups of patients.The ongoing third trial, ARCADIA, tests the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in participants with cryptogenic ischemic stroke and atrial cardiopathy, as defined by 1 of 3 cardiac markers: P-wave terminal force >5000 µV× ms in ECG lead V1, serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) >250 pg/mL, and left atrial diameter index ≥3 cm/m2 on echocardiogram (Table 1).11Since 2018, when NINDS renewed funding of the network for 5 additional years, the number of funded trials and active clinical trial sites in the network increased markedly (Table 1). At the time of the COVID pandemic, 6 trials were recruiting: MOST (Multi-Arm Optimization of Stroke Thrombolysis), Sleep SMART (Sleep for Stroke Management and Recovery Trial), I-ACQUIRE (Infant ACQUIRE), TRANSPORT2 (Transcranial Direct Current Stimulation for Post-Stroke Motor Recovery A Phase II Study), ARCADIA, and ARCADIA-CSI (ARCADIA-Cognition and Silent Infarcts). In addition, 2 trials had been ready to open enrollment, ASPIRE (Anticoagulation for Stroke Prevention and Recovery After Intracerebral Hemorrhage) and SATURN (Statins Use in Intracerebral Patient). The FASTEST trial (FVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time) was funded on February 28, 2020, with enrollment planned to start in the early fall.Educational CoreSince the beginning of StrokeNet, the educational mission of the network has been a priority. StrokeNet includes yearly-designated StrokeNet clinical research fellowships at each regional center across the United States, and our Educational Core leadership coordinates this education program and mentoring process across the network. The activities and outcomes of educational core have been detailed in an article published recently in Stroke.12Imaging CoreSince the beginning of StrokeNet, the imaging core has been providing support to the clinical trial design in terms of imaging protocols and homogenization of imaging across sites. In addition, StrokeNet offers a common mechanism for central collection of images for all clinical trials. Combined with the use of common data elements in the coding of these images, the central collection of images allows for increased standardization of imaging across trials and for pooled analyses in the future. Such efficiencies are highly desirable considering the high cost of imaging in clinical trials.Impact of COVID-19 on NIH StrokeNetCOVID-19 represents a once-in-a-lifetime event that profoundly affects all clinical research now and going forward. Stroke research has unique challenges since patients often have communication issues requiring consent from legally authorized representatives, severely ill stroke patients may require intubation, stroke patients often move across several healthcare settings before returning home, and stroke patients frequently need transportation to health care or research facilities. Organized research networks like the NIH StrokeNet are uniquely positioned to address unforeseen challenges such as COVID-19. The response to an extraordinary situation can be coordinated across all trials and trial sites in the network while communicating best practices, innovative approaches, and the changing environment among the national principal investigators of all ongoing trials, as well as site principal investigators from hundreds of recruitment sites.By February, recruitment had been accelerating in many of the trials, some of which had just begun enrollment in the prior months, and was poised to start in 2 of the trials. The events surrounding COVID-19 impacted clinical trials by closing clinical research activities at many institutions nationally and internationally in March 2020. The NIH StrokeNet leadership met regularly with the central institutional review board leadership to discuss the situation across the network. Concerns pertinent to the rapidly evolving situation included the safety of current and potential research participants and research staff, as well as the potential impact of research activities to the clinical care and resources available to potential COVID-19 patients. On March 13, detailed guidance regarding the COVID situation from StrokeNet leadership, the central institutional review board, and the NINDS was sent to StrokeNet trial investigators (Table 2).Table 2. Initial Guidance From StrokeNet Leadership to Trial PIs Regarding COVID-19Guidance to Trial SitesMonitoring and following all CDC and local recommendations regarding good hygiene, avoidance of major gatherings (social distancing), travel, etcAdherence to local institution recommendations regarding research in the COVID-19 environment, including screening or enrollment into research trials. Some institutions had already suspended screening and enrollment, whereas others had notMaintenance of patient follow-up for those participants already enrolled in trials and use of telemedicine and telephone interactions whenever possible to obtain study data. Per FDA guidance, these changes could happen even if the protocol had not yet been amendedAmendment of all trial protocols to allow for remote patient visits for outcomes, study medications, etc, for situations like COVID-19 and communication of the amendment to the CIRBUse of an unblinded assessor as needed for those studies that require blinded outcome assessors if designated person was not availableCompletion of outcome assessments outside of the prescribed windows as needed (because of illness)For studies requiring study medication, mailing of study medication, even if not detailed in protocolFor trials requiring physical or hands-on therapy and in-clinic or at-home visits, suspension of therapy when a patient or therapist is COVID-19 positive or is possibly infected and restarting therapy only when the participant is no longer contagiousCrafting of plans by trial PIs regarding COVID-19 issues unique to their trialSuspension of any in-person StrokeNet meetings until the situation has changed to minimal riskCommunication of COVID-19 infection in a study patient or study investigator to the trial PIs as allowed by HIPAACDC indicates Center for Disease Control; CIRB, central institutional review board; COVID-19, coronavirus disease 2019; FDA, Food and Drug Administration; HIPAA, Health Insurance Portability and Accountability Act; and PIs, principal investigators.In consideration of the safety of patients, study investigators, and the clinical resources and personnel needed for clinical care of COVID-19, and after discussions with the StrokeNet leadership, all study enrollment was suspended in StrokeNet trials on March 24 while maintaining follow-up of participants, to the extent possible, within ongoing trials. While the primary goal of suspension of enrollment was safety of relevant parties during the peak of the pandemic, StrokeNet leadership and the trial principal investigators used this time to redesign processes and protocols within the trials that would enable safely restarting enrollment in the trials as quickly as possible, while recognizing the local conditions and requirements at a given site. Within a month of suspension of enrollment, 2 trials had submitted a plan to the central institutional review board for reopening enrollment, and a template letter for restarting trials was provided to all trial principal investigators to assist them in crafting a trial-specific plan and request to central institutional review board to restart enrollment (http://nihstrokenet.org/documents).Table 3 describes some of the specific impacts of COVID-19 and the proposed solutions by the network to address these issues. Solutions include increased and innovative use of telemedicine and digital technologies, flexible approaches for interactions of the study teams with participants, a centralized approach to electronic and remote consent across all trial sites rather than each individual site, innovative approaches to online survey and focus groups for studies using exemption from informed consent, clear masks for therapy with infants and young children to allow perception of facial expressions, and reconsideration of all study processes including timing of enrollment from onset and outcome assessments. Some of these changes had already been initiated earlier in the year but were accelerated by the COVID-19 pandemic. Many of the changes will be positive changes for our clinical research platform going forward.Table 3. COVID-19 Impact on Trials and Implemented SolutionsCOVID-19 Impact on TrialsPlanned and Implemented SolutionsProtocols required in-person screening and enrollmentInvestigator-participant interactions by telemedicine; multiple methods of remote consent including eConsent, as well as a centralized eConsent process and platform for entire trial and not just at individual sites (REDcap database).Protocols required in-person visits for distribution of study medication (eg, ARCADIA, ASPIRE)Direct shipping of study medication to patient homes with revised timeline and assurance of patient's receipt of study medication.Protocols required in-person outcome assessments (eg, MOST, I-ACQUIRE, and TRANSPORT2).Outcomes by telemedicine and recorded video. Audio recording if video not possible. Therapy trials that require in-person assessment must adopt precautions that mirror recommendations for COVID-19 patient care.Central cognitive assessment for ARCADIA-CSI trial had to be onsite at institutionTechnology amended to allow cognitive assessment from test administrators' homes.Centralized laboratory for trial closed for non-COVID research activities (eg, ARCADIA, SATURN)Discussions with laboratories to consider restart receipt of laboratory samples (rate-limiting step for trials to reopen).Therapy trials that require close-contact multisession rehabilitation therapy or the use of tools and devices in combination with the rehabilitation therapy on a daily basis (eg, TRANSPORT2 and I-ACQUIRE)Plan for use of daily COVID-19 screening questionnaire to assess risk of exposure and infection and PPE (eg, masks and gloves) for both staff (eg, therapists/trainers) and study subjects that mirror clinical recommendations. Disinfect/clean the rehabilitation and assessment tools and machines/devices (such as tDCS/TMS/MRI) after each visit.Inability for children (ages 8 mo to 3 y) to see faces of therapists wearing facemasks during therapy (I-ACQUIRE)Transparent masks designed for the hearing-impaired purchased for trial to allow visualization of facial expressions to help with communication and therapy.Inability to do typical in-person focus groups or to survey large groups of community members in person as required by exception from informed consent or EFIC (FASTEST)Centralized online survey tool using REDCap for all participating sites in the United States that can be used for several sites within same community. Online focus groups—regionally and nationally. Discussion with Advarra the CIRB for FASTEST regarding implementation.Sleep SMART–Concern for aerosolization of viral particles by CPAPProvision of clinical guidance to participants regarding mitigation of risk to household members, circumstances under which CPAP use may merit review with local physician.Less study activity at trial sites with suspension of enrollmentMaintenance of screening for potent
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