TAKE-HOLD: Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03327909
• Collaborator: Satellite Healthcare (Other)
• Enrollment: 131
• Locations: 2
• Arms: 2
• Actual Duration (Months): 17
• Patients Per Site: 65.5
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
ESRD; Hemodialysis Complication; Blood Pressure	Behavioral: TAKE vs. HOLD	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Cluster randomized parallel group trialCluster randomized parallel group trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis
• Actual Study Start Date: Jul 16, 2018
• Actual Primary Completion Date: Dec 14, 2019
• Actual Study Completion Date: Dec 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAKE Participants in TAKE units will be advised to take all antihypertensive medications as prescribed, including on the morning of dialysis.	Behavioral: TAKE vs. HOLD; 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.
Experimental: HOLD 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; 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.

Outcome Measures

Primary Outcome Measures

1. Intradialytic Hypotension [4-week intervention period]

   Number of participants with ≥30% of dialysis sessions with symptomatic or asymptomatic IDH.

Secondary Outcome Measures

1. Poorly controlled pre-dialysis blood pressure [4-week intervention period]

   Number of participants with ≥30% of dialysis sessions with pre-dialysis systolic BP > 160 mm Hg

2. Dialysis Tolerability [4-week intervention period]

   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.

Other Outcome Measures

1. 44-hour ambulatory blood pressure [Final week of the 4-week intervention period]

   Compare the number of hours spent in the desired systolic BP range of 110-150 mm Hg in patients in TAKE versus HOLD units. We will also compare the number of patients who demonstrate nocturnal dipping patterns of BP in the TAKE and HOLD units.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥ 18 years

2. On in-center thrice weekly hemodialysis

3. Dialysis start time in the morning

4. Taking at least one antihypertensive medication

Exclusion Criteria:

1. Initiation of hemodialysis within previous 90 days

2. Inability to provide informed consent

3. Currently participating in another clinical trial (intervention study)

4. 2 unexcused missed dialysis sessions in the previous 30 days

5. Documented heart failure with reduced ejection fraction (left ventricular ejection fraction < 40%)

6. 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

7. End-stage liver disease

8. Planned kidney transplant within the next 90 days

9. Planned dialysis modality switch (to home hemodialysis, peritoneal dialysis, nocturnal hemodialysis) within the next 90 days

10. Pregnancy, currently trying to become pregnant

11. Active infection requiring antibiotic, antifungal or antiviral therapies

12. Any factors judged by the treatment team to be likely to limit adherence to the interventions

13. Active alcohol or substance abuse within the last 12 months

14. Plans to move outside of the treatment area within in the next 90 days

15. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Satellite Health Care	Menlo Park	California	United States	94025
2	Satellite Health Care	San Carlos	California	United States	94070

Sponsors and Collaborators

• Stanford University
• Satellite Healthcare

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chang TI, Tatoian ET, Montez-Rath ME, Chertow GM. Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized Trial. Kidney360. 2021 Sep 16;2(11):1752-1760. doi: 10.34067/KID.0001922021. eCollection 2021 Nov 25.

• Responsible Party: Tara I-Hsin Chang, Assistant Professor of Medicine (Nephrology), Stanford University
• ClinicalTrials.gov Identifier: NCT03327909
• Other Study ID Numbers: TAKE-HOLD
• First Posted: Nov 1, 2017
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tara I-Hsin Chang, Assistant Professor of Medicine (Nephrology), Stanford University: Intradialytic Hypotension, Hypertension, Ambulatory Blood Pressure

Study Results

No Results Posted as of Aug 23, 2022