Intensification of Blood Pressure Lowering Therapeutics Based on Diuretics Versus Usual Management for Uncontrolled Hypertension IN Patients With Moderate to Severe Chronic Kidney Disease

NCT05732727 | Recruiting Phase 3

• 2 other identifiers: DR2103202022-501494-39-00
• Study Type: interventional
• Target: 720
• Locations: 1 country
• Sites: 40

Brief Summary

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.

Conditions

Chronic Kidney Disease(CKD); Uncontrolled Hypertension

Outcome Measures

Primary Outcomes (4)

• End stage kidney disease

  The primary endpoint is a time to event outcome, considering the following composite endpoint: * End stage kidney disease * eGFR decline of at least 40% * Cardiovascular events among myocardial infarction, heart failure, hospitalization and stroke * All cause mortality

  Up to 36 months

• eGFR decline of at least 40%

  The primary endpoint is a time to event outcome, considering the following composite endpoint: * End stage kidney disease * eGFR decline of at least 40% * Cardiovascular events among myocardial infarction, heart failure, hospitalization and stroke * All cause mortality

  Up to 36 months

• Cardiovascular events

  The primary endpoint is a time to event outcome, considering the following composite endpoint: * End stage kidney disease * eGFR decline of at least 40% * Cardiovascular events among myocardial infarction, heart failure, hospitalization and stroke * All cause mortality

  Up to 36 months

• All cause mortality

  The primary endpoint is a time to event outcome, considering the following composite endpoint: * End stage kidney disease * eGFR decline of at least 40% * Cardiovascular events among myocardial infarction, heart failure, hospitalization and stroke * All cause mortality

  Up to 36 months

Secondary Outcomes (10)

• Time to end-stage kidney disease

  Up to 36 months

• Time to eGFR decrease of at leat 40%

  Up to 36 months

• Time to the first cardiovascular event among myocardial infarction, heart failure, hospitalization and stroke

  Up to 36 months

• All-cause mortality

  Up to 36 months

• Change from baseline in blood pressure

  From baseline and up to 36 months

Study Arms (2)

Experimental group

EXPERIMENTAL

Antihypertensive algorithm based on diuretics agents : the clinicians will adjust the drug therapy according to the antihypertensive algorithm based on diuretics agents.

Drug: Antihypertensive algorithm

Control group

ACTIVE COMPARATOR

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.

Drug: Standard of care

Interventions

Antihypertensive algorithm DRUG

Antihypertensive algorithm based on diuretics agents

Experimental group

Standard of care DRUG

standard of care management for antihypertensive therapy intensification

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female \>=18 years with a clinical frailty score ≤5 for patient aged over 80
• 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 in combination with or in the event of intolerance to ACE inhibitors or ARBs.
• Uncontrolled office BP
• Uncontrolled office BP (\>140 and/or 90 mmHg) confirmed by home blood pressure monitoring (\>135 and/or 85 mmHg) or Day-time Ambulatory Blood Pressure Monitoring
• Participant covered by or entitled to social security
• Written informed consent obtained from the participant

You may not qualify if:

• 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
• Symptomatic 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)

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (40)

Department of Nephrology, University Hospital of Angers

Angers, 49933, France

RECRUITING

Department of Nephrology, University Hospital of Bordeaux

Bordeaux, 33000, France

RECRUITING

AUB Santé foundation, Brest

Brest, 29200, France

RECRUITING

Department of Nephrology, University Hospital of Brest

Brest, 29200, France

RECRUITING

Department of Nephrology, Hospital of Chalon-sur-Saône

Chalon-sur-Saône, France

RECRUITING

Department of Nephrology, Hospital of Chartres

Chartres, 28630, France

RECRUITING

Department of Nephrology, University Hospital of Clermont-Ferrand

Clermont-Ferrand, 63001, France

RECRUITING

Department of Nephrology, Hospital of Colmar

Colmar, 68024, France

RECRUITING

Department of Nephrology, University Hospital of Grenoble

Grenoble, 38043, France

RECRUITING

Department of Nephrology, Hospital of Haguenau

Haguenau, 67500, France

RECRUITING

Department of Nephrology, Departemental Hospital of Vendée

La Roche-sur-Yon, 85925, France

RECRUITING

ECHO Santé Association, Le Mans

Le Mans, 72100, France

RECRUITING

Department of Nephrology, Hospital of Le Puy en Velay

Le Puy-en-Velay, 43012, France

RECRUITING

Department of Nephrology, University Hospital of Lille

Lille, 59000, France

RECRUITING

Department of Nephrology, University Hospital of Limoges

Limoges, 87042, France

RECRUITING

AUB Santé foundation, Lorient

Lorient, 56100, France

RECRUITING

Department of Nephrology, University Hospital of Lyon

Lyon, 69003, France

RECRUITING

Department of Nephrology, University Hospital of Marseille

Marseille, 13005, France

RECRUITING

Department of Nephrology, Regional Hospital of Metz

Metz, 57085, France

RECRUITING

Department of Nephrology, Régional Hospital of Mulhouse

Mulhouse, 68100, France

RECRUITING

Department of Nephrology, University Hospital of Nantes

Nantes, 44093, France

RECRUITING

ECHO Santé Association, Nantes

Nantes, 44402, France

RECRUITING

Department of Nephrology, University Hospital of Nîmes

Nîmes, 30029, France

RECRUITING

Department of Nephrology, Hospital of Orléans

Orléans, 45067, France

RECRUITING

Department of Nephrology, European Hospital Georges Pompidou, AP-HP

Paris, 75015, France

ACTIVE NOT RECRUITING

Department of Nephrology, Necker Hospital, AP-HP

Paris, 75015, France

RECRUITING

Department of Nephrology, Bichat Hospital, AP-HP

Paris, 75018, France

RECRUITING

Department of Nephrology, Tenon Hospital, AP-HP

Paris, 75020, France

ACTIVE NOT RECRUITING

Department of Nephrology, Hospital of Perpignan

Perpignan, 66046, France

RECRUITING

Department of Nephrology, University Hospital of Reims

Reims, 51092, France

RECRUITING

Department of Nephrology, University Hospital of Rennes

Rennes, 35033, France

RECRUITING

Department of Nephrology, Hospital of Roubaix

Roubaix, 59100, France

RECRUITING

Department of Nephrology, University Hospital of Rouen

Rouen, 76230, France

RECRUITING

Department of Nephrology, University Hospital of Saint Etienne

Saint-Etienne, 42270, France

RECRUITING

ECHO Santé Association, Saint Herblain

Saint-Herblain, 44819, France

ACTIVE NOT RECRUITING

Department of Nephrology, Hospital of Saint Malo

St-Malo, 35400, France

RECRUITING

Department of Nephrology, Hospital of Strasbourg

Strasbourg, 67000, France

RECRUITING

Department of Nephrology, University Hospital of Tours

Tours, 37044, France

RECRUITING

Department of Nephrology, Hospital of Valenciennes

Valenciennes, 59322, France

RECRUITING

Department of Nephrology, University Hospital of Nancy

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Bénédicte Sautenet, MD

  University Hospital, Tours

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bénédicte Sautenet, MD

CONTACT

02.34.37.96.86; benedicte.sautenet@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The very nature of the intervention assessed prevents any form of blinding, neither for care providers, nor for patients. However, the primary outcome is a composite outcome of events which we plan to adjudicate. As a consequence, the primary outcome will be blindly assessed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cluster randomized controlled

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 17, 2023
• Study Start: March 28, 2023
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: December 1, 2025

Record last verified: 2025-11

Locations

FR (40)