Dataset Information

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

ABSTRACT:

Background

Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established.

Methods

To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients.

Results

The trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care.

Conclusions

Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery.

SUBMITTER: Dember LM

PROVIDER: S-EPMC6493975 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

Dember Laura M LM Lacson Eduardo E Brunelli Steven M SM Hsu Jesse Y JY Cheung Alfred K AK Daugirdas John T JT Greene Tom T Kovesdy Csaba P CP Miskulin Dana C DC Thadhani Ravi I RI Winkelmayer Wolfgang C WC Ellenberg Susan S SS Cifelli Denise D Madigan Rosemary R Young Amy A Angeletti Michael M Wingard Rebecca L RL Kahn Christina C Nissenson Allen R AR Maddux Franklin W FW Abbott Kevin C KC Landis J Richard JR

Journal of the American Society of Nephrology : JASN 20190418 5

<h4>Background</h4>Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established.<h4>Methods</h4>To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ...[more]

PMID: 31000566

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Project description:BackgroundCluster randomized trials (CRTs) are trials in which intact groups such as hemodialysis centers or shifts are randomized to treatment or control arms. Pragmatic CRTs have been promoted as a promising trial design for nephrology research yet may also pose ethical challenges. While randomization occurs at the cluster level, the intervention and data collection may vary in a CRT, challenging the identification of research participants. Moreover, when a waiver of patient consent is granted by a research ethics committee, there is an open question as to whether and to what degree patients should be notified about ongoing research or be provided with a debrief regarding the nature and results of the trial upon completion. While empirical and conceptual research exploring ethical issues in pragmatic CRTs has begun to emerge, there has been limited discussion with patients, families, or caregivers of patients undergoing hemodialysis.ObjectiveTo explore with patients and families with experience of hemodialysis research the challenges raised by different approaches to designing pragmatic CRTs in hemodialysis. Specifically, their perceptions of (1) the use of a waiver of consent, (2) notification processes and information provided to participants, and (3) any other concerns about cluster randomized designs in hemodialysis.DesignFocus group and interview discussions of hypothetical clinical trial designs.SettingFocus groups and interviews were conducted in-person or via videoconference or telephone.ParticipantsPatient partners in hemodialysis research, defined as patients with personal experience of dialysis or a family member who had experience supporting a patient receiving hemodialysis, who have been actively involved in discussions to advise a research team on the design, conduct, or implementation of a hemodialysis trial.MethodsParticipants were invited to participate in focus groups or individual discussions that were audio recorded with consent. Recorded interviews were transcribed verbatim prior to analysis. Transcripts were analyzed using a thematic analysis approach.ResultsTwo focus groups, three individual interviews, and one interview involving a patient and family member were conducted with 17 individuals between February 2019 and May 2020. Participants expressed support for approaches that emphasized patient choice. Disclosure of patient-relevant risks and information were key themes. Both consent and notification processes served to generate trust, but bypassing patient choice was perceived as undermining this trust. Participants did not dismiss the option of a waiver of consent. They were, however, more restrictive in their views about when a waiver of consent may be acceptable. Patient partners were skeptical of claims to impracticability based on costs or the time commitments for staff.LimitationsAll participants were from Canada and had been involved in the design or conduct of a trial, limiting the degree to which results may be extrapolated.ConclusionsGiven the preferences of participants to be afforded the opportunity to decide about trial participation, we argue that investigators should thoroughly investigate approaches that allow participants to make an informed choice regarding trial participation. In keeping with the preference for autonomous choice, there remains a need to further explore how consent approaches can be designed to facilitate clinical trial conduct while meeting their ethical requirements. Finally, further work is needed to define the limited circumstances in which waivers of consent are appropriate.

Project description:Purpose of the conferenceHemodialysis is a life-sustaining treatment for patients with end-stage kidney disease. However, patients on dialysis continue to face poor quality of life and short life expectancies. Despite this, the nephrology community conducts the fewest randomized controlled trials of any medical discipline, relying instead on expert opinion to guide many aspects of hemodialysis care. There is a need to conduct high-quality pragmatic randomized controlled trials in hemodialysis to drive evidence-based practice. To this end, the Innovative Clinical Trials in Hemodialysis Centers initiative, with the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, funded the development of 6 pragmatic trial protocols. Gardener's Grove 2023 created a space to support the development of these trials and increase awareness and knowledge of past, ongoing, and future innovative, pragmatic, randomized controlled registry trials embedded in routine hemodialysis care. This report summarizes the proceedings of this conference.Sources of informationThe conference included 6 panel presentations, each featuring an overview of a new pragmatic trial followed by expert panel feedback from patient partners, nephrologists, researchers, and health care providers. The conference also included 10 educational sessions led by clinicians and researchers with experience in the fields of kidney medicine and clinical trials.MethodsGardener's Grove 2023 was a 4-day virtual conference held in March of 2023. Recordings of all the conference presentations were later published on the Gardener's Grove website and are summarized in the Supplemental Appendix of this report.Key findingsThe conference brought together 118 Canadian and international researchers, patients, and health care providers to collaborate on 6 pragmatic trials intended to test interventions to improve hemodialysis care. The proposed trials included (1) PREventing FracturEs in REnal Disease (PREFERRED), (2) DIALysis with EXpanded solute removal (DIALEX), (3) Sodium fOr diaLysis oUTcome rEduction (SOLUTE), (4) Finding the right blood pressure target for patients on dialysis, (5) DIuretic Use in patients with Residual renal function on hemodialysis (DIURESED), and (6) Lower vs higher dialysate bicarbonate concentration in patients receiving hemodialysis (Dial-Bicarb). All of these interventions were widely supported and received valuable feedback from panelists and conference attendees. The education sessions focused on various design and execution elements of pragmatic, randomized controlled registry trials embedded in routine care.LimitationsThe conference could have been improved by streamlining session topics and pacing, allowing additional time for discussions, strengthening online network opportunities, and improving survey response rates. A follow-up conference is planned to take place in a few years, and the coordinators will aim to implement these changes.ImplicationsGardener's Grove 2023 successfully created a space for patients, researchers, and health care providers to support the development of 6 new pragmatic trials in hemodialysis care. Since Gardener's Grove 2023, several of these trials have secured CIHR funding, obtained ethics approval, and are actively preparing to launch their interventions.

Project description:BackgroundAlthough naloxone prevents opioid overdose deaths, few patients prescribed opioids receive naloxone, limiting its effectiveness in real-world settings. Barriers to naloxone prescribing include concerns that naloxone could increase risk behavior and limited time to provide necessary patient education.ObjectiveTo determine whether pharmacy-based naloxone co-dispensing affected opioid risk behavior. Secondary objectives were to assess if co-dispensing increased naloxone acquisition, increased patient knowledge about naloxone administration, and affected opioid dose and other substance use.DesignCluster randomized pragmatic trial of naloxone co-dispensing.SettingSafety-net health system in Denver, Colorado, between 2017 and 2020.ParticipantsSeven pharmacies were randomized. Pharmacy patients (N=768) receiving opioids were followed using automated data for 10 months. Pharmacy patients were also invited to complete surveys at baseline, 4 months, and 8 months; 325 survey participants were enrolled from November 15, 2017, to January 8, 2019.InterventionIntervention pharmacies implemented workflows to co-dispense naloxone while usual care pharmacies provided usual services.Main measuresSurvey instruments assessed opioid risk behavior; hazardous drinking; tobacco, cannabis, and other drug use; and knowledge. Naloxone dispensings and opioid dose were evaluated using pharmacy data among pharmacy patients and survey participants. Intention-to-treat analyses were conducted using generalized linear mixed models accounting for clustering at the pharmacy level.Key resultsOpioid risk behavior did not differ by trial group (P=0.52; 8-month vs. baseline adjusted risk ratio [ARR] 1.07; 95% CI 0.78, 1.47). Compared with usual care pharmacies, naloxone dispensings were higher in intervention pharmacies (ARR 3.38; 95% CI 2.21, 5.15) and participant knowledge increased (P=0.02; 8-month vs. baseline adjusted mean difference 1.05; 95% CI 0.06, 2.04). There was no difference in other substance use by the trial group.ConclusionCo-dispensing naloxone with opioids effectively increased naloxone receipt and knowledge but did not increase self-reported risk behavior.Trial registrationRegistered at ClinicalTrials.gov ; Identifier: NCT03337100.

Project description:ImportanceLate predictions of hospitalized patient deterioration, resulting from early warning systems (EWS) with limited data sources and/or a care team's lack of shared situational awareness, contribute to delays in clinical interventions. The COmmunicating Narrative Concerns Entered by RNs (CONCERN) Early Warning System (EWS) uses real-time nursing surveillance documentation patterns in its machine learning algorithm to identify patients' deterioration risk up to 42 hours earlier than other EWSs.ObjectiveTo test our a priori hypothesis that patients with care teams informed by the CONCERN EWS intervention have a lower mortality rate and shorter length of stay (LOS) than the patients with teams not informed by CONCERN EWS.DesignOne-year multisite, pragmatic controlled clinical trial with cluster-randomization of acute and intensive care units to intervention or usual-care groups.SettingTwo large U.S. health systems.ParticipantsAdult patients admitted to acute and intensive care units, excluding those on hospice/palliative/comfort care, or with Do Not Resuscitate/Do Not Intubate orders.InterventionThe CONCERN EWS intervention calculates patient deterioration risk based on nurses' concern levels measured by surveillance documentation patterns, and it displays the categorical risk score (low, increased, high) in the electronic health record (EHR) for care team members.Main outcomes and measuresPrimary outcomes: in-hospital mortality, LOS; survival analysis was used. Secondary outcomes: cardiopulmonary arrest, sepsis, unanticipated ICU transfers, 30-day hospital readmission.ResultsA total of 60 893 hospital encounters (33 024 intervention and 27 869 usual-care) were included. Both groups had similar patient age, race, ethnicity, and illness severity distributions. Patients in the intervention group had a 35.6% decreased risk of death (adjusted hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.532-0.778; P<.0001), 11.2% decreased LOS (adjusted incidence rate ratio, 0.914; 95% CI, 0.902-0.926; P<.0001), 7.5% decreased risk of sepsis (adjusted HR, 0.925; 95% CI, 0.861-0.993; P=.0317), and 24.9% increased risk of unanticipated ICU transfer (adjusted HR, 1.249; 95% CI, 1.093-1.426; P=.0011) compared with patients in the usual-care group.Conclusions and relevanceA hospital-wide EWS based on nursing surveillance patterns decreased in-hospital mortality, sepsis, and LOS when integrated into the care team's EHR workflow.Trial registrationClinicalTrials.gov Identifier: NCT03911687.

Project description:BackgroundCentral nervous system (CNS) active medications have been consistently linked to falls in older people. However, few randomized trials have evaluated whether CNS-active medication reduction reduces falls and fall-related injuries. The objective of the Reducing CNS-active Medications to Prevent Falls and Injuries in Older Adults (STOP-FALLS) trial is to test the effectiveness of a health-system-embedded deprescribing intervention focused on CNS-active medications on the incidence of medically treated falls among community-dwelling older adults.MethodsWe will conduct a pragmatic, cluster-randomized, parallel-group, controlled clinical trial within Kaiser Permanente Washington to test the effectiveness of a 12-month deprescribing intervention consisting of (1) an educational brochure and self-care handouts mailed to older adults prescribed one or more CNS-active medications (aged 60 + : opioids, benzodiazepines and Z-drugs; aged 65 + : skeletal muscle relaxants, tricyclic antidepressants, and antihistamines) and (2) decision support for their primary health care providers. Outcomes are examined over 18-26 months post-intervention. The primary outcome is first incident (post-baseline) medically treated fall as determined from health plan data. Our sample size calculations ensure at least 80% power to detect a 20% reduction in the rate of medically treated falls for participants receiving care within the intervention (n = 9) versus usual care clinics (n = 9) assuming 18 months of follow-up. Secondary outcomes include medication discontinuation or dose reduction of any target medications. Safety outcomes include serious adverse drug withdrawal events, unintentional overdose, and death. We will also examine medication signetur fields for attempts to decrease medications. We will report factors affecting implementation of the intervention.DiscussionThe STOP-FALLS trial will provide new information about whether a health-system-embedded deprescribing intervention that targets older participants and their primary care providers reduces medically treated falls and CNS-active medication use. Insights into factors affecting implementation will inform future research and healthcare organizations that may be interested in replicating the intervention.Trial registrationClinicalTrial.gov NCT05689554. Registered on 18 January 2023, retrospectively registered.

Project description:BackgroundWhile audit & feedback (A&F) is an effective implementation intervention, the design elements which maximize effectiveness are unclear. Partnering with a healthcare quality advisory organization already delivering feedback, we conducted a pragmatic, 2 × 2 factorial, cluster-randomized trial to test the impact of variations in two factors: (A) the benchmark used for comparison and (B) information framing. An embedded process evaluation explored hypothesized mechanisms of effect.MethodsEligible physicians worked in nursing homes in Ontario, Canada, and had voluntarily signed up to receive the report. Groups of nursing homes sharing physicians were randomized to (A) physicians' individual prescribing rates compared to top-performing peers (the top quartile) or the provincial median and (B) risk-framed information (reporting the number of patients prescribed high-risk medication) or benefit-framed information (reporting the number of patients not prescribed). We hypothesized that the top quartile comparator and risk-framing would lead to greater practice improvements. The primary outcome was the mean number of central nervous system-active medications per resident per month. Primary analyses compared the four arms at 6 months post-intervention. Factorial analyses were secondary. The process evaluation comprised a follow-up questionnaire and semi-structured interviews.ResultsTwo hundred sixty-seven physicians (152 clusters) were randomized: 67 to arm 1 (median benchmark, benefit framing), 65 to arm 2 (top quartile benchmark, benefit framing), 75 to arm 3 (median benchmark, risk framing), and 60 to arm 4 (top quartile benchmark, risk framing). There were no significant differences in the primary outcome across arms or for each factor. However, engagement was low (27-31% of physicians across arms downloaded the report). The process evaluation indicated that both factors minimally impacted the proposed mechanisms. However, risk-framed feedback was perceived as more actionable and more compatible with current workflows, whilst a higher target might encourage behaviour change when physicians identified with the comparator.ConclusionsRisk framing and a top quartile comparator have the potential to achieve change. Further work to establish the strategies most likely to enhance A&F engagement, particularly with physicians who may be most likely to benefit from feedback, is required to support meaningfully addressing intricate research questions concerning the design of A&F.Trial registrationClinicalTrials.gov, NCT02979964 . Registered 29 November 2016.

Dataset Information

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

Background

Methods

Results

Conclusions

Publications

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

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