Thiazide Diuretics for Hypertension in Kidney Transplant Recipients Using Tacrolimus

Phase 3

Completed

• Conditions: Kidney Transplantation; Hypertension
• Interventions: Drug: Chlorthalidone; Drug: Amlodipine

• Registration Number: NCT02644395
• Lead Sponsor: Erasmus Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01-18
• Primary Completion: 2015-12-17
• Study First Submitted: 2015-12-28
• Study First Submitted QC: 2015-12-29
• Study First Posted: 2015-12-31
• Study Completion: 2016-12-19
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-15
• Last Update Posted: 2017-06-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Chlorthalidone	Chlorthalidone	Testing new indication for approved drug
Amlodipine	Amlodipine	Current treatment of choice

Primary Outcome Measures

Name	Time	Method
Average daytime SBP	8 weeks

Secondary Outcome Measures

Name	Time	Method
Side effects	8 weeks
Laboratory parameters	8 weeks

Trial Locations

Locations (1)

ErasmusMC; 🇳🇱 Rotterdam, Netherlands