Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis

Study Overview
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Brief Summary
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For patients with kidney failure requiring hemodialysis treatment, sometimes the blood pressure will drop too low during dialysis. In an effort to prevent that from occurring, patients are frequently told to skip doses of their blood pressure medications. However, whether this actually prevents blood pressure drops during dialysis, and whether it may cause more uncontrolled high blood pressure is unknown. TAKE-HOLD will study the effect of taking or holding blood pressure medication on blood pressure for patients on hemodialysis.

Detailed Description
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High blood pressure (BP) is a major modifiable risk factor for cardiovascular disease, and upwards of 90% of patients with end- stage renal disease (ESRD) have high BP. Appropriate BP management, therefore, is a fundamental part of patient care in ESRD, yet the question of when best to take antihypertensive medications relative to the hemodialysis treatment session remains unanswered. Many patients on hemodialysis suffer from an abrupt fall in BP during the dialysis session (i.e., intradialytic hypotension [IDH]), a phenomenon that is associated with numerous adverse outcomes. In an attempt to minimize IDH, patients are often told to withhold antihypertensive medications prior to hemodialysis, and current guidelines suggest taking antihypertensive medications at night to minimize IDH. However, there are no data regarding the safety of these antihypertensive medication timing strategies, or whether these strategies are effective in reducing IDH.

Official Title
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Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis

Conditions
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ESRD, Hemodialysis Complication, Blood Pressure

Intervention / Treatment
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* Behavioral: TAKE vs. HOLD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years On in-center thrice weekly hemodialysis Dialysis start time in the morning Taking at least one antihypertensive medication Exclusion Criteria: Initiation of hemodialysis within previous 90 days Inability to provide informed consent Currently participating in another clinical trial (intervention study) >2 unexcused missed dialysis sessions in the previous 30 days Documented heart failure with reduced ejection fraction (left ventricular ejection fraction < 40%) Cardiovascular event (e.g. myocardial infarction, stroke, heart failure) or procedure (e.g., coronary artery bypass, peripheral arterial bypass grafting, carotid artery procedures, aortic procedures) or hospitalization for unstable angina within the previous 90 days End-stage liver disease Planned kidney transplant within the next 90 days Planned dialysis modality switch (to home hemodialysis, peritoneal dialysis, nocturnal hemodialysis) within the next 90 days Pregnancy, currently trying to become pregnant Active infection requiring antibiotic, antifungal or antiviral therapies Any factors judged by the treatment team to be likely to limit adherence to the interventions Active alcohol or substance abuse within the last 12 months Plans to move outside of the treatment area within in the next 90 days Other medical, psychiatric, or behavioral factors that in the judgement of the study team may interfere with study participation or the ability to follow the intervention protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cluster randomized parallel group trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAKE<br>Participants in TAKE units will be advised to take all antihypertensive medications as prescribed, including on the morning of dialysis. | Behavioral: TAKE vs. HOLD<br>* All participants will be told to take once daily antihypertensive medications at night. Timing of other antihypertensive medication administration will differ depending on whether the participant is randomized to the TAKE or HOLD arm.<br>|
| Experimental: HOLD<br>Participants in the HOLD units will advised to hold the dose of the antihypertensive medications prior to the dialysis session on the morning of the dialysis days. Participants can choose whether they wish to take the antihypertensive medication that was held at any time after the dialysis session has ended. | Behavioral: TAKE vs. HOLD<br>* All participants will be told to take once daily antihypertensive medications at night. Timing of other antihypertensive medication administration will differ depending on whether the participant is randomized to the TAKE or HOLD arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intradialytic Hypotension | Number of participants with ≥30% of dialysis sessions with symptomatic or asymptomatic IDH. | 4-week intervention period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Poorly controlled pre-dialysis blood pressure | Number of participants with ≥30% of dialysis sessions with pre-dialysis systolic BP > 160 mm Hg | 4-week intervention period | 
| Dialysis Tolerability | Number of participants with ≥30% of dialysis sessions with post-dialysis weight > prescribed dry weight or delivered length of dialysis < prescribed length. We will also assess dialysis symptoms using the Dialysis Symptom Index. | 4-week intervention period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intradialytic Hypotension, Hypertension, Ambulatory Blood Pressure