UH3 Project: Time to Reduce Mortality in End-Stage Renal Disease (TiME)
Overview
Principal Investigator:
Sponsoring Institution: University of Pennsylvania
Collaborators:
NIH Institute Providing Oversight: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Program Official: Paul Kimmel, MD (NIDDK)
Project Scientist: Kevin Abbott, MD, MPH (NIDDK)
ClinicalTrials.gov Identifier: NCT02019225
Study Locations: Dialysis facilities throughout the United States
Trial Status: Terminated
Trial Summary
Study question and significance: Although maintenance hemodialysis has been used for end-stage kidney disease for more than 50 years, there is uncertainty about the best approaches for many of the fundamental aspects of treatment, including the optimal duration of hemodialysis sessions. The objectives of the TiME trial were to evaluate the effects on mortality and hospitalization rates of hemodialysis session durations that are longer than many patients in the United States currently receive, and to establish approaches for embedding randomized clinical trials into the routine delivery of dialysis care.
Design and setting: Cluster randomized trial conducted in 266 dialysis units operated by 2 large dialysis provider organizations. Dialysis units were randomized in a 1:1 ratio to either the intervention or usual care.
Intervention and methods: Facilities randomized to the intervention adopted a default hemodialysis session duration of ≥ 4.25 hours, and facilities randomized to usual care had no trial-driven approach to session duration. Enrollment was restricted to patients new to dialysis (incident patients). The primary outcome was mortality, and the major secondary outcomes were hospitalization rate and quality of life. The trial relied entirely on clinical personnel and clinically acquired data.
Findings: The trial enrolled 7035 patients with demographic and clinical characteristics that matched those of the overall US hemodialysis patient population. The trial was discontinued after a median follow-up of 1.1 years because there was an insufficient difference in mean hemodialysis session duration between the intervention group and the usual care group. There was no reduction in mortality or hospitalization rate in the intervention group compared with usual care.
Conclusions and relevance: Although the highly pragmatic design allowed efficient participant enrollment, data acquisition, and adherence monitoring, intervention uptake was insufficient to determine whether use of longer hemodialysis sessions improves outcomes. Effective approaches for engaging clinical personnel and patients are required to evaluate interventions fully embedded in care delivery
Data and Resource Sharing
- TiME_Data_Dictionary_V1
TiME Data Dictionary
- TiME Protocol
TiME Protocol
- Consent-Info-Sheets-for-Study-Sites-20130920
TiME Consent Info Sheets for Study Sites
- TiME_Dember_UH3 follow-up (2)
TiME Ethics and Regulatory Documentation - UH3 Project Updates
Featured Interviews
Dr. Dember discusses the TiME Trial.
News and Interviews
- News_Applying PRECIS Ratings to Collaboratory Pragmatic Trials
January 16, 2016: Applying PRECIS Ratings to Collaboratory Pragmatic Trials
- News_Collaboratory PIs Give Advice to New Pragmatic Trials
November 1, 2019: Collaboratory PIs Give Advice to New Pragmatic Trials
- News_PIs of Completed NIH Collaboratory Demonstration Projects Share Accomplishments
July 14, 2020: PIs of Completed NIH Collaboratory Trials Share Accomplishments
- News_TiME Trial Confirms Feasibility of Embedding Large Pragmatic Trials in Clinical Care
April 22, 2019: TiME Trial Confirms Feasibility of Embedding Large Pragmatic Trials in Clinical Care
- PI-Tips-Interview-2017
Written Interview: An Interview With NIH Collaboratory Trials PIs
- Dember-Larson-Interview-8-27-15
Written Interview: Interview with Drs. Laura Dember and Eric Larson
Publications
- Lee et al Can J Kidney Health Dis 2019
Cultivating innovative pragmatic cluster-randomized registry trials embedded in hemodialysis care: workshop proceedings from 2018
- Dember J Am Soc Nephrol 2019
A pragmatic step forward: AKI and beyond
- Flythe et al J Am Soc Nephrol 2019
Cultivating a research-ready dialysis community
- Flythe et al Am J Kidney Dis 2018
Perspectives on research participation and facilitation among dialysis patients, clinic personnel, and medical providers: a focus group study
- Baigent et al Kidney Int 2017
Challenges in conducting clinical trials in nephrology: conclusions from a Kidney Disease-Improving Global Outcomes (KDIGO) Controversies Conference
- Perl et al Clin J Am Soc Nephrol 2017
The use of a multidimensional measure of dialysis adequacy-moving beyond small solute kinetics
- Bonventre et al Clin J Am Soc Nephrol 2014
The kidney research national dialogue: gearing up to move forward
- Berns and Dember J Am Soc Nephrol 2013
Can frequent hemodialysis be too frequent?
- Richesson et al J Am Med Inform Assoc 2021
Enhancing the use of EHR systems for pragmatic embedded research: lessons from the NIH Health Care Systems Research Collaboratory
- Living Textbook Chapter_Which PCTs Should Have a DMC
Living Textbook Chapter: Which PCTs Should Have a DMC?
- Living Textbook_The Embedded Pragmatic Trials Ecosystem
Living Textbook: The Embedded Pragmatic Clinical Trial Ecosystem
- TiME Study Snapshot
TiME Study Snapshot
- Goldstein et al Am J Kidney Dis 2019
Ethical issues in pragmatic cluster-randomized trials in dialysis facilities
- Dember et al J Am Soc Nephrol 2019
TiME Main Outcome Paper
- Living Textbook Chapter_Data Sharing and Embedded Research
Living Textbook Chapter: Data Sharing Solutions for Embedded Research
- Courtright et al Trials 2017
Willingness to participate in pragmatic dialysis trials: the importance of physician decisional autonomy and consent approach
- Living Textbook Chapter_Statistical Design Considerations
Living Textbook Chapter: Experimental Designs and Randomization Schemes: Statistical Design Considerations
- Living Textbook_Alternative Approaches to Disclosure and Authorization
Living Textbook Chapter: Alternative Approaches to Disclosure and Authorization
- Dember et al J Am Soc Nephrol 2016
Pragmatic trials in maintenance dialysis: perspectives from the Kidney Health Initiative
- Kraybill et al AJOB Empir Bioeth 2016
Empirical Ethics Supplement Publication: Patient and physician views about protocolized dialysis treatment in randomized trials and clinical care
Presentations
- SC-2019-Completed-TiME
Time to Reduce Mortality in End-Stage Renal Disease (TiME)
- Presentation_ABATE_TiME_PROVEN_ARM_2019_c
Pragmatic Trial Design Panel (AcademyHealth 2019)
- Workshop on the Design and Analysis of PCTs_Panel 4_Unique Considerations
Workshop on the Design and Analysis of PCTs: Panel 4: Unique Considerations
- 13.-Dember_TiME-Trial-Barriers.Lessons_REVISED
TiME Trial: Challenges and Insights
- GR-Slides-09-15-17
Who to Include in a Pragmatic Trial? It Depends (GR Slides 2017)
- GR-Video-09-15-17
Who to Include in a Pragmatic Trial? It Depends (GR Video 2017)
- Abstract_TiME_2017_c
Primary Results of the TiME Trial (Abstract 2017)
- Panel-4-_Sustainability_Dissemination-Workshop_24MAY2017
Panel 4: Sustainability Dissemination Workshop
- Dember-SC-May-2017
Barriers, Challenges, and Lessons Learned from TiME
- GR-Video-06-10-16
Pragmatic Trials in Dialysis: What’s Next after the TiME Trial? (GR Video 2016)
- GR-Slides-06-10-16
Pragmatic Trials in Dialysis: What’s Next after the TiME Trial? (GR Slides 2016)
- Workshop_Ethical and Regulatory Issues_Panel 1_Options for Altered Consent
Ethical and Regulatory Issues of PCTs Workshop: Panel 1 - Options for Altered Consent and the Importance of Minimal Risk Determination
- DemberLessonsLearnedTiME5 9 16Posting
DemberLessonsLearnedTiME5 9 16Posting
- Dember Data Sharing Considerations for the TiME Trial
DemberData Sharing Considerations for the TiME Trial
- TiME_Dember_4-20-15
Update on TiME at Steering Committee Meeting
- GR Slides 02-06-15
The TiME Trial: Moving from Planning to Implementation (GR Slides 2015)
- GR-Video-02-06-15
The TiME Trial From Planning to Implementation (GR Video 2015)
- TiME Trial Lessons Learned_082014POST THESE
Lessons learned (so far) from the TiME Trial
- TiME Data Sharing_Dember_2-24-2014
TiME Data Sharing Discussion
- Decision Autonomy in PCTs Supplement_Dember2-14-2014
Decision Autonomy in Pragmatic Clinical Trials—Supplement to TiME Presentation at Steering Committee Meeting
- GR-Video-09-27-13
Pragmatic Trials for Uncommon Conditions (GR Video 2013)
- GR Slides 09-27-13
Pragmatic Trials for Uncommon Conditions (GR Slides 2013)
- GR-Video-02-22-13
Time to Reduce Mortality in End-Stage Renal Disease (TiME) (GR Video 2013)
- GR Slides 02-22-13
Time to Reduce Mortality in End-State Renal Disease (GR Slides 2013)