Thiazide Diuretics for Hypertension in Kidney Transplant Recipients Using Tacrolimus

Hypertension Clinical Trial

— TT  

Official title:

Thiazide Diuretics for Hypertension in Kidney Transplant Recipients Using Tacrolimus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02644395
• Other study ID #: MEC-2012-417
• Status: Completed
• Phase: Phase 3
• First received: December 28, 2015
• Last updated: June 15, 2017
• Start date: January 18, 2013
• Est. completion date: December 19, 2016

Study information

• Verified date: June 2017
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 19, 2016
• Est. primary completion date: December 17, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Kidney Transplantation

Intervention

Drug:
• Chlorthalidone
Drug
• Amlodipine
Drug

Locations

Country	Name	City	State
Netherlands	ErasmusMC	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average daytime SBP		8 weeks
Secondary	Laboratory parameters		8 weeks
Secondary	Side effects		8 weeks