NCT02644395

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
49

participants targeted

Target at below P25 for phase_3 hypertension

Timeline
Completed

Started Jan 2013

Longer than P75 for phase_3 hypertension

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 18, 2013

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 17, 2015

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

December 28, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 31, 2015

Completed
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 19, 2016

Completed
Last Updated

June 16, 2017

Status Verified

June 1, 2017

Enrollment Period

2.9 years

First QC Date

December 28, 2015

Last Update Submit

June 15, 2017

Conditions

HypertensionKidney Transplantation

Outcome Measures

Primary Outcomes (1)

  • Average daytime SBP

    8 weeks

Secondary Outcomes (2)

  • Laboratory parameters

    8 weeks

  • Side effects

    8 weeks

Study Arms (2)

Amlodipine

ACTIVE COMPARATOR

Current treatment of choice

Drug: Amlodipine

Chlorthalidone

EXPERIMENTAL

Testing new indication for approved drug

Drug: Chlorthalidone

Interventions

ChlorthalidoneDRUG

Drug

Chlorthalidone
AmlodipineDRUG

Drug

Amlodipine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Kidney transplant recipients using tacrolimus
  • Average daytime SBP \> 140 mm Hg (ABPM)
  • eGFR \> 30 ml/min (MDRD)

You may not qualify if:

  • Use of glucocorticoids, co-trimoxazole, diuretics
  • Pregnancy
  • Serum sodium \< 136, serum potassium \< 3.5
  • Proteinuria \> 1 g/day

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

ErasmusMC

Rotterdam, Netherlands

Location

Related Publications (2)

  • 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.

    PMID: 28259499BACKGROUND

  • 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.

    PMID: 39082471DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

ChlorthalidoneAmlodipine

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

BenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsBenzophenonesPhthalimidesImidesKetonesSulfonesSulfur CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDihydropyridinesPyridinesHeterocyclic Compounds, 1-Ring

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

December 28, 2015

First Posted

December 31, 2015

Study Start

January 18, 2013

Primary Completion

December 17, 2015

Study Completion

December 19, 2016

Last Updated

June 16, 2017

Record last verified: 2017-06

Locations

NL(1)