- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05732727
Intensification of Blood Pressure Lowering Therapeutics Based on Diuretics Versus Usual Management for Uncontrolled Hypertension IN Patients With Moderate to Severe Chronic Kidney Disease (THINK)
October 25, 2023 updated by: University Hospital, Tours
Intensification of Blood Pressure Lowering Therapeutics Based on Diuretics Versus Usual Management for Uncontrolled Hypertension IN Patients With Moderate to Severe Chronic Kidney Disease: an Open Label, a Cluster Randomized Controlled, Phase 3 Trial
Chronic kidney disease (CKD) is a major public health issue worldwide.
Hypertension is the first risk factor in patients with CKD for mortality, cardiovascular disease and end-stage renal disease.
It's now well established that lowering blood pressure (BP) reduces renal and cardiovascular complications in this high-risk population.
In the general population, in addition to lifestyle interventions, the strategy to initiate and escalate a BP-lowering drug treatment is well described.
The drug therapies recommended to achieve optimal BP control in the general population are the following: blockers of the renin-angiotensin system (angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)), diuretics (thiazides and thiazide-like diuretics), and calcium channel blockers.
For patients with CKD, the guidelines advise to start the BP-lowering agent with ACEi or ARB, but then, there is no strong evidence to support the preferential use of any particular agent in controlling BP and the results of clinical trials are discordant.
In the NephroTest cohort, a French cohort of patients with CKD stage 1 to 5, among 2015 patients, 1782 had hypertension, only 54% had a diuretic and 44% had uncontrolled hypertension.
In this cohort, extracellular fluid (ECF) overload was an independent determinant of hypertension, uncontrolled hypertension and apparent treatment resistant hypertension.
In the same cohort, ECF overload was independently associated with end-stage kidney disease and death.
Our hypothesis is that patients with CKD and uncontrolled hypertension are fluid overloaded and that the second line of treatment after an ACEi or an ARB should be a diuretic.
We hypothesize that a specific algorithm to lower BP in patients with moderate to severe CKD based on diuretics will be more effective in term of cardiovascular event, mortality and evolution to end-stage kidney disease as compared to standard of care.
Study Overview
Status
Recruiting
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
720
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Bénédicte Sautenet, MD
- Phone Number: +33 02.34.37.96.86
- Email: benedicte.sautenet@gmail.com
Study Locations
-
-
-
Angers, France, 49933
- Recruiting
- Department of Nephrology, University Hospital of Angers
-
Contact:
- Martin PLANCHAIS, MD
-
Principal Investigator:
- Martin PLANCHAIS, MD
-
Bordeaux, France, 33000
- Active, not recruiting
- Department of Nephrology, University Hospital of Bordeaux
-
Brest, France, 29200
- Active, not recruiting
- AUB Santé foundation, Brest
-
Brest, France, 29200
- Recruiting
- Department of Nephrology, University Hospital of Brest
-
Contact:
- Yannick LE MEUR, MD-PhD
-
Principal Investigator:
- Yannick LE MEUR, MD-PhD
-
Chalon-sur-Saône, France
- Recruiting
- Department of Nephrology, Hospital of Chalon-sur-Saône
-
Contact:
- Magali LOUIS, MD
-
Principal Investigator:
- Magali LOUIS, MD
-
Chartres, France, 28630
- Recruiting
- Department of Nephrology, Hospital of Chartres
-
Principal Investigator:
- Catherine ALBERT, MD
-
Contact:
- Catherine ALBERT, MD
-
Clermont-Ferrand, France, 63001
- Recruiting
- Department of Nephrology, University Hospital of Clermont-Ferrand
-
Contact:
- Julien ANIORT, MD
-
Principal Investigator:
- Julien ANIORT, MD
-
Colmar, France, 68024
- Recruiting
- Department of Nephrology, Hospital of Colmar
-
Contact:
- Alexandre KLEIN, MD
-
Principal Investigator:
- Alexandre KLEIN, MD
-
Grenoble, France, 38043
- Active, not recruiting
- Department of Nephrology, University Hospital of Grenoble
-
Haguenau, France, 67500
- Active, not recruiting
- Department of Nephrology, Hospital of Haguenau
-
La Roche-sur-Yon, France, 85925
- Recruiting
- Department of Nephrology, Departemental Hospital of Vendée
-
Contact:
- Anne Hélène QUERARD, MD
-
Principal Investigator:
- Anne Hélène QUERARD, MD
-
Le Mans, France, 72100
- Active, not recruiting
- ECHO Santé Association, Le Mans
-
Le Puy-en-Velay, France, 43012
- Recruiting
- Department of Nephrology, Hospital of Le Puy en Velay
-
Principal Investigator:
- Marc BOUILLER, MD
-
Contact:
- Marc BOUILLER, MD
-
Limoges, France, 87042
- Recruiting
- Department of Nephrology, University Hospital of Limoges
-
Contact:
- Fatouma TOURE, MD-PhD
-
Principal Investigator:
- Fatima TOURE, MD-PhD
-
Lyon, France, 69003
- Active, not recruiting
- Department of Nephrology, University Hospital of Lyon
-
Marseille, France, 13005
- Active, not recruiting
- Department of Nephrology, University Hospital of Marseille
-
Metz, France, 57085
- Recruiting
- Department of Nephrology, Regional Hospital of Metz
-
Contact:
- Maël LATEB, MD
-
Principal Investigator:
- Maël LATEB, MD
-
Mulhouse, France, 68100
- Recruiting
- Department of Nephrology, Régional Hospital of Mulhouse
-
Contact:
- François CHANTREL, MD
-
Principal Investigator:
- François CHANTREL, MD
-
Nantes, France, 44093
- Recruiting
- Department of Nephrology, University Hospital of Nantes
-
Contact:
- Caroline GOURRAUD VERCEL, MD
-
Principal Investigator:
- Caroline GOURRAUD VERCEL, MD
-
Nantes, France, 44402
- Active, not recruiting
- ECHO Santé Association, Nantes
-
Nîmes, France, 30029
- Active, not recruiting
- Department of Nephrology, University Hospital of Nîmes
-
Paris, France, 75015
- Active, not recruiting
- Department of Nephrology, European Hospital Georges Pompidou, AP-HP
-
Paris, France, 75015
- Active, not recruiting
- Department of Nephrology, Necker Hospital, AP-HP
-
Paris, France, 75018
- Active, not recruiting
- Department of Nephrology, Bichat Hospital, AP-HP
-
Paris, France, 75020
- Active, not recruiting
- Department of Nephrology, Tenon Hospital, AP-HP
-
Perpignan, France, 66046
- Active, not recruiting
- Department of Nephrology, Hospital of Perpignan
-
Reims, France, 51092
- Active, not recruiting
- Department of Nephrology, University Hospital of Reims
-
Rennes, France, 35033
- Active, not recruiting
- Department of Nephrology, University Hospital of Rennes
-
Roubaix, France, 59100
- Recruiting
- Department of Nephrology, Hospital of Roubaix
-
Contact:
- Thomas GUINCESTRE, MD
-
Principal Investigator:
- Thomas GUINCESTRE, MD
-
Rouen, France, 76230
- Active, not recruiting
- Department of Nephrology, University Hospital of Rouen
-
Saint-Herblain, France, 44819
- Active, not recruiting
- ECHO Santé Association, Saint Herblain
-
Saint-Malo, France, 35400
- Active, not recruiting
- Department of Nephrology, Hospital of Saint Malo
-
Saint-Étienne, France, 42270
- Recruiting
- Department of Nephrology, University Hospital of Saint Etienne
-
Contact:
- Christophe MARIAT, MD-PhD
-
Principal Investigator:
- Christophe MARIAT, MD-PhD
-
Tours, France, 37044
- Recruiting
- Department of Nephrology, University Hospital of Tours
-
Contact:
- Bénédicte SAUTENET, MD
-
Principal Investigator:
- Bénédicte SAUTENET, MD
-
Valenciennes, France, 59322
- Recruiting
- Department of Nephrology, Hospital of Valenciennes
-
Contact:
- Marc ULRICH, MD
-
Principal Investigator:
- Marc ULRICH, MD
-
vandoeuvre les Nancy, France, 54511
- Active, not recruiting
- Department of Nephrology, University Hospital of Nancy
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Male or female >=18 years and <80 years of age
- Advanced or moderate chronic kidney disease (eGFR 15 to 44.9 mL/min/1.73m² using CKD-EPI formula)
- Arterial hypertension treated with at least one blood pressure lowering drug therapy among blockers of the renin-angiotensin system (ACEi or ARB), at the maximal posology tolerated by the patients stable since at least one month. Other blood pressure lowering drug therapies are tolerated.
- Uncontrolled office BP (>140 and/or 90 mmHg) confirmed by home blood pressure monitoring (>135/85 mmHg)
- Participant covered by or entitled to social security
- Written informed consent obtained from the participant
Exclusion Criteria:
- Patient following any measures of legal presentation
- Pregnant or breastfeeding woman
- woman of childbearing without a highly effective contraceptive measure (combined or progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device or intrauterine hormone-releasing system)
- Clinical signs of hypovolemia
- Orthostatic hypotension
- Hyponatremia (<130 mmol/L)
- Dyskalemia (<3,5 mmol/L or >5,5 mmol/L)
- Major adverse cardiovascular event during the last three months: myocardial infarction, heart failure hospitalization, stroke
- Current medical history of cancer requiring chemotherapy
- Solid organ transplantation
- Two or more diuretic agents (loop diuretic, thiazides and thiazide-like diuretics)
- Mineralocorticoid receptor antagonists
- Autosomal dominant polycystic kidney disease treated with Tolvaptan
- Contraindication to diuretics involved in the algorithm
- Severe heart failure (NYHA III_IV)
- Cirrhosis Child B-C
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Experimental group
Antihypertensive algorithm based on diuretics agents : the clinicians will adjust the drug therapy according to the antihypertensive algorithm based on diuretics agents.
|
Antihypertensive algorithm based on diuretics agents
|
Active Comparator: Control group
Standard of care : the clinicians will adapt the antihypertensive strategy according to his own standard of care which can be pharmacological or non-pharmacological therapies.
|
standard of care management for antihypertensive therapy intensification
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
End stage kidney disease
Time Frame: Up to 36 months
|
The primary endpoint is a time to event outcome, considering the following composite endpoint:
|
Up to 36 months
|
eGFR decline of at least 40%
Time Frame: Up to 36 months
|
The primary endpoint is a time to event outcome, considering the following composite endpoint:
|
Up to 36 months
|
Cardiovascular events
Time Frame: Up to 36 months
|
The primary endpoint is a time to event outcome, considering the following composite endpoint:
|
Up to 36 months
|
All cause mortality
Time Frame: Up to 36 months
|
The primary endpoint is a time to event outcome, considering the following composite endpoint:
|
Up to 36 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to end-stage kidney disease
Time Frame: Up to 36 months
|
All components of the composite endpoint will be assessed separately
|
Up to 36 months
|
Time to eGFR decrease of at leat 40%
Time Frame: Up to 36 months
|
All components of the composite endpoint will be assessed separately
|
Up to 36 months
|
Time to the first cardiovascular event among myocardial infarction, heart failure, hospitalization and stroke
Time Frame: Up to 36 months
|
All components of the composite endpoint will be assessed separately
|
Up to 36 months
|
All-cause mortality
Time Frame: Up to 36 months
|
All components of the composite endpoint will be assessed separately
|
Up to 36 months
|
Change from baseline in blood pressure
Time Frame: From baseline and up to 36 months
|
Systolic and diastolic blood pressure at months 3 and 6 then every 6 months (home blood pressure monitoring and office blood pressure measurement),
|
From baseline and up to 36 months
|
Proportion of patients with controlled blood pressure
Time Frame: 24 months
|
Proportion of patients with controlled blood pressure at 2 years (PA< 135/85mmHg with home blood pressure monitoring)
|
24 months
|
Change from baseline in glomerular filtration rate
Time Frame: From baseline and up to 36 months
|
Change from baseline in glomerular filtration rate estimated by CKD-EPI formula at months 3 and 6 then every 6 months
|
From baseline and up to 36 months
|
Proportion of patients who used at least one diuretic
Time Frame: Up to 36 months
|
Up to 36 months
|
|
Change from baseline in quality of life
Time Frame: From baseline and up to 36 months
|
Change from baseline in quality of life assessed by PROMIS-29 survey each year
|
From baseline and up to 36 months
|
Change from baseline in proteinuria (g/d) or proteinuria /creatinuria (g/g)
Time Frame: From baseline and up to 36 months
|
Change from baseline in proteinuria (g/d) or proteinuria /creatinuria (g/g) at months 3 and 6 then every 6 months
|
From baseline and up to 36 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Bénédicte Sautenet, MD, University Hospital, Tours
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 28, 2023
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
March 1, 2027
Study Registration Dates
First Submitted
February 8, 2023
First Submitted That Met QC Criteria
February 8, 2023
First Posted (Actual)
February 17, 2023
Study Record Updates
Last Update Posted (Actual)
October 30, 2023
Last Update Submitted That Met QC Criteria
October 25, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Urologic Diseases
- Disease Attributes
- Renal Insufficiency
- Chronic Disease
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Hypertension
- Kidney Diseases
- Renal Insufficiency, Chronic
- Antihypertensive Agents
Other Study ID Numbers
- DR210320
- 2022-501494-39-00 (Other Identifier: EU CT)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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