Thiazide Diuretics for Hypertension in Kidney Transplant Recipients Using Tacrolimus

NCT ID: NCT02644395

Last Updated: 2017-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-18
• Study Completion Date: 2016-12-19

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.

Conditions

Hypertension; Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Amlodipine

Current treatment of choice

Group Type: ACTIVE_COMPARATOR

Amlodipine

Intervention Type: DRUG

Drug

Chlorthalidone

Testing new indication for approved drug

Group Type: EXPERIMENTAL

Chlorthalidone

Intervention Type: DRUG

Drug

Interventions

Chlorthalidone

Drug

Intervention Type: DRUG

Amlodipine

Drug

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ewout Hoorn

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

ErasmusMC

Rotterdam, , Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 28259499 (View on PubMed)

Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.

Reference Type: DERIVED

PMID: 39082471 (View on PubMed)

Other Identifiers

MEC-2012-417

Identifier Type: -

Identifier Source: org_study_id