TT: Thiazide Diuretics for Hypertension in Kidney Transplant Recipients Using Tacrolimus

• Sponsor: Erasmus Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02644395
• Collaborator: (none)
• Enrollment: 49
• Location: 1
• Arms: 2
• Actual Duration (Months): 47
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Background: Calcineurin inhibitors (CNIs) are the most commonly used immunosuppressive drugs to prevent rejection after kidney transplantation. However, the efficacy of preventing rejection comes at the cost of important side-effects. Among the most common side-effects is hypertension. Hypertension after kidney transplantation is clinically relevant, because it increases the risk of cardiovascular disease and is associated with increased graft loss and recipient mortality. The mechanism of CNI-induced hypertension is incompletely understood and, therefore, the treatment is currently empiric. These and other investigators recently showed that CNIs cause salt-sensitive hypertension by activating a sodium transporter in the kidney, namely the thiazide-sensitive sodium chloride cotransporter.

Hypothesis: The investigators hypothesize that thiazide diuretics are non-inferior to calcium channel blockers (CCBs) (currently usually the treatment of choice) for the treatment of CNI-induced hypertension.

Objective: To compare the blood pressure response to thiazide diuretics and CCBs in patients with CNI-induced hypertension.

Study design: Single-center, randomized cross-over trial.

Study population: Kidney transplant recipients with a good functioning allograft (eGFR > 30 ml/min) who are hypertensive (daytime systolic blood pressure > 140 mm Hg) and who do not have proteinuria (< 1 g/day).

Intervention: Patients will be randomized to receive chlorthalidone (12.5 mg once daily, if needed titrated to 25 mg once daily) or amlodipine (5 mg once daily, if needed titrated to 10 mg once daily).

Main study parameters/endpoints: 24-hour blood pressure recording.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Both drugs have long been registered for the treatment of hypertension. The side-effect profile of both drugs is considered to be equal. The burden of the study for the patients are blood pressure measurements using 30-minute automated blood pressure measurement and 24-hour ambulatory blood pressure measurement.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Kidney Transplantation	Drug: Chlorthalidone; Drug: Amlodipine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Thiazide Diuretics for Hypertension in Kidney Transplant Recipients Using Tacrolimus
• Actual Study Start Date: Jan 18, 2013
• Actual Primary Completion Date: Dec 17, 2015
• Actual Study Completion Date: Dec 19, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Amlodipine Current treatment of choice	Drug: Amlodipine; Drug
Experimental: Chlorthalidone Testing new indication for approved drug	Drug: Chlorthalidone; Drug

Outcome Measures

Primary Outcome Measures

1. Average daytime SBP [8 weeks]

Secondary Outcome Measures

1. Laboratory parameters [8 weeks]

2. Side effects [8 weeks]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Kidney transplant recipients using tacrolimus

• Average daytime SBP > 140 mm Hg (ABPM)

• eGFR > 30 ml/min (MDRD)

Exclusion Criteria:

• Use of glucocorticoids, co-trimoxazole, diuretics

• Pregnancy

• Serum sodium < 136, serum potassium < 3.5

• Proteinuria > 1 g/day

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ErasmusMC	Rotterdam		Netherlands

Sponsors and Collaborators

• Erasmus Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Moes AD, Hesselink DA, van den Meiracker AH, Zietse R, Hoorn EJ. Chlorthalidone Versus Amlodipine for Hypertension in Kidney Transplant Recipients Treated With Tacrolimus: A Randomized Crossover Trial. Am J Kidney Dis. 2017 Jun;69(6):796-804. doi: 10.1053/j.ajkd.2016.12.017. Epub 2017 Mar 1.

• Responsible Party: Ewout Hoorn, Associate Professor, Erasmus Medical Center
• ClinicalTrials.gov Identifier: NCT02644395
• Other Study ID Numbers: MEC-2012-417
• First Posted: Dec 31, 2015
• Last Update Posted: Jun 16, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Hypertension; Amlodipine; Chlorthalidone

Study Results

No Results Posted as of Jun 16, 2017