Clinical trial NCT02628366: Major Outcomes With Personalized Dialysate TEMPerature
Official title: Major Outcomes With Personalized Dialysate TEMPerature: Pragmatic, Registry-Based, Cluster Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Kidney Diseases
End-Stage Kidney Disease
Hemodialysis
Keywords: Cluster randomized Controlled Trial
Personalized Dialysate Temperature
Cooler Dialysate Temperature
Mortality
Cardiovascular Events
Myocardial Infarction
Ischemic Stroke
Congestive Heart Failure
Dialysis Solutions
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Population Health Research Institute
name: Ottawa Hospital Research Institute
name: Dialysis Clinic, Inc.
name: Cancer Care Ontario
name: Institute for Clinical Evaluative Sciences
name: The Kidney Foundation of Canada
name: Canadian Institutes of Health Research (CIHR)
First posted: 2015-12-11
Enrollment: 84
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: People with failed kidneys need an artificial kidney machine (called dialysis) to remove toxins and extra fluid from the body. Most patients receive dialysis treatments at a hospital three times a week. During treatment, a patient's blood pressure may drop, causing dizziness and muscle cramping. Repeated drops in blood pressure can also injure the heart and brain. Over time, this can lead to heart attacks, strokes, and sometimes death due to cardiovascular causes. New research shows that cooling the temperature of the dialysis fluid (called dialysate) can reduce heart and brain injury. In most hospitals, all patients' dialysate temperature is set at 36.5 ºC (to match body temperature). In a study of 73 patients, we showed that reducing the dialysate temperature by 0.5 ºC below body temperature protected the heart and brain from injury \[1,2\]. We now want to test this simple, safe, low-cost intervention in a large study with \~7500 dialysis patients in Ontario. We can lower the dialysate temperature on dialysis machines in Ontario at no added cost. This intervention has the potential to reduce many hospitalizations and deaths in Ontario, and relieve suffering in patients with kidney failure.

Detailed description: 1. Statement of the health problem or issue

   Dialysis is a life-saving treatment for patients with kidney failure. However, over 20% of patients die within one year of starting dialysis from heart disease or stroke.

   One reason that so many dialysis patients die from heart diseases and strokes may be related to the dialysis treatment itself. During dialysis, blood pressure often drops, and the flow of blood and oxygen to the heart and brain is reduced. Over time, this can cause significant damage to vital organs and result in heart attacks, strokes, and even death due to cardiovascular-related causes.

   Our team was the first to show that the heart and brain become starved of blood and oxygen during dialysis. We and others have shown that lowering the temperature of dialysis (to just below the patient's own body temperature) improves blood flow and protects the heart and brain during dialysis. We will now determine if this method can prevent heart attacks and strokes in a large population of dialysis patients.
2. Objective of your project

   The purpose of this study is to test the effect of outpatient hemodialysis centers randomized to (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol for 4 years on cardiovascular-related death and hospitalizations.
3. How will you undertake your work?

   We will conduct a cluster randomized controlled trial. Our study will include \~7500 dialysis patients in 84 dialysis centres across Ontario. The name of this study is MyTEMP. Patients in 42 of the 84 dialysis centres will be in the treatment group and they will receive personalized dialysis (0.5-0.9ºC below their measured body temperature). Patients in the other 42 centres will be in the control group and will receive standard dialysis at a fixed temperature of 36.5ºC. This study will last for four years. At the end of four years, we will compare the rate of cardiovascular-related deaths, heart attacks, strokes, and heart failure in the treatment and control groups.
4. What is unique/innovative about your project?

   We usually need to study a large number of patients in a clinical trial to reliably understand the effects of treatment. Normally, a study with 7500 patients would cost more than $15 million dollars to conduct; however, our study will provide a reliable answer to the question being asked and cost less than $2 million. This is because we will use data that is already being collected by our healthcare system. For example, when a patient is hospitalized for a heart attack or stroke, this information is recorded in a secure healthcare database. We will be able to analyze these healthcare data at the end of the study (and link patient outcomes to the type of dialysis treatment received (i.e. treatment or control)). This innovative study design means that our study will be much larger (but cost much less) than a traditional clinical trial.

   This pragmatic trial includes all patients who receive chronic in-centre hemodialysis patients in participating Ontario centres. High-risk patients with multiple comorbidities, including cognitive impairments or disabilities, who are often excluded from trials because of their high-risk status are eligible for participation in the MyTEMP trial. By including patients from a variety of medical, ethnic, geographic, and socioeconomic backgrounds, the results of our trial should be broadly generalizable.
5. What is the impact of the proposed research?

Currently, many patients worldwide receive hemodialysis with a dialysate temperature of 36.5ºC to 37.0ºC. Lowering the dialysate temperature below a core body temperature is a promising intervention that has the potential to reduce the risk of cardiovascular-related mortality and major adverse cardiovascular events in patients on hemodialysis.

At four years of follow-up, our trial is powered to detect a minimum 20% hazard rate difference in the composite outcome of time to first cardiovascular-related mortality or hospitalization for major cardiovascular events among centres that use a temperature-reduced personalized hemodialysis protocol compared with centres that use a standard-temperature hemodialysis protocol.

Eligibility criteria: This pragmatic cluster randomized controlled trial has only two inclusion criteria:

Inclusion Criteria:

* The hemodialysis centre must have cared for a minimum of 15 outpatients being treated with maintenance in-centre hemodialysis on January 1st, 2017.
* The medical director of the hemodialysis centre (who acted as the centre's gatekeeper) must have been willing for their centre to adopt the randomly allocated dialysate temperature protocol for the duration of the trial.

Exclusion Criteria:

* The centre cares for less than 15 patients being treated with conventional in-centre hemodialysis.

Primary outcomes:
measure: Composite outcome of cardiovascular-related mortality or major cardiovascular event
timeFrame: Four Years
Secondary outcomes:
measure: Key secondary outcome: Between-group mean difference in the intradialytic drop of systolic blood pressure.
timeFrame: Four Years
measure: Composite outcome of all-cause mortality or major cardiovascular event
timeFrame: Four Years
measure: All-cause mortality
timeFrame: Four Years
measure: Hospitalization for non-fatal myocardial infarction
timeFrame: Four Years
measure: Hospitalization for non-fatal congestive heart failure
timeFrame: Four Years
measure: Hospitalization for non-fatal ischemic stroke
timeFrame: Four Years
measure: Cardiovascular-related mortality
timeFrame: Four Years
Other outcomes:
measure: Composite of All-Cause emergency department visits or all-cause hospitalizations (repeated measure)
timeFrame: Four Years
measure: All-Cause emergency department visits (repeated measures)
timeFrame: Four Years
measure: All-cause hospitalizations (repeated measure)
timeFrame: Four years
measure: Hospital encounter with lower limb amputation
timeFrame: Four Years
measure: Hospital encounter with a major fall or fracture
timeFrame: Four Years
measure: Intradialytic hypotension
timeFrame: Four years
measure: Intradialytic hypotension alternate definition #1
timeFrame: Four years
measure: Intradialytic hypotension alternate definition #2
timeFrame: Four years
measure: Intradialytic hypotension alternate definition #3
timeFrame: Four years
measure: Intradialytic hypotension alternate definition #4
timeFrame: Four years
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: London Health Sciences Centre
name: Amit X Garg, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London Health Sciences Centre
name: Christopher W McIntyre, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Presseau J, Mutsaers B, Al-Jaishi AA, Squires J, McIntyre CW, Garg AX, Sood MM, Grimshaw JM; Major outcomes with personalized dialysate TEMPerature (MyTEMP) investigators. Barriers and facilitators to healthcare professional behaviour change in clinical trials using the Theoretical Domains Framework: a case study of a trial of individualized temperature-reduced haemodialysis. Trials. 2017 May 22;18(1):227. doi: 10.1186/s13063-017-1965-9.
citation: Ward JM, Getchell L, Garg AX; MyTEMP Investigators. Patient and caregiver involvement in a multicentre clustered hemodialysis trial. CMAJ. 2018 Nov 7;190(Suppl):S32-S33. doi: 10.1503/cmaj.180403. No abstract available.
citation: MyTEMP writing committee. Personalised cooler dialysate for patients receiving maintenance haemodialysis (MyTEMP): a pragmatic, cluster-randomised trial. Lancet. 2022 Nov 12;400(10364):1693-1703. doi: 10.1016/S0140-6736(22)01805-0. Epub 2022 Nov 4.
citation: Dixon SN, Sontrop JM, Al-Jaishi A, Killin L, McIntyre CW, Anderson S, Bagga A, Benjamin D, Blake P, Devereaux PJ, Iliescu E, Jain A, Lok CE, Nesrallah G, Oliver MJ, Pandeya S, Sood MM, Tam P, Wald R, Walsh M, Zwarenstein M, Garg AX. MyTEMP: Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial. Can J Kidney Health Dis. 2021 Aug 27;8:20543581211041182. doi: 10.1177/20543581211041182. eCollection 2021.
citation: Al-Jaishi AA, McIntyre CW, Sontrop JM, Dixon SN, Anderson S, Bagga A, Benjamin D, Berry D, Blake PG, Chambers L, Chan PCK, Delbrouck N, Devereaux PJ, Ferreira-Divino LF, Goluch R, Gregor L, Grimshaw JM, Hanson G, Iliescu E, Jain AK, Lok CE, Mustafa RA, Nathoo B, Nesrallah GE, Oliver MJ, Pandeya S, Parmar MS, Perkins D, Presseau J, Rabin E, Sasal J, Shulman T, Sood MM, Steele A, Tam P, Tascona D, Wadehra D, Wald R, Walsh M, Watson P, Wodchis W, Zager P, Zwarenstein M, Garg AX. Major Outcomes With Personalized Dialysate TEMPerature (MyTEMP): Rationale and Design of a Pragmatic, Registry-Based, Cluster Randomized Controlled Trial. Can J Kidney Health Dis. 2020 Feb 5;7:2054358119887988. doi: 10.1177/2054358119887988. eCollection 2020.