Impact of Reducing Antihypertensive Treatment on Mortality in Frail Subjects With Low Systolic Blood Pressure (SBP).

NCT ID: NCT03453268

Last Updated: 2025-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1048 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-02
• Study Completion Date: 2024-08-15

Brief Summary

The investigators hypothesize that a gradual reduction in antihypertensive treatment in medical-social institutions patients with low systolic blood pressure (SBP) can improve survival through a controlled increase in SBP and a decrease in secondary morbidity due to 'overmedication'.

Accordingly, the investigators propose a randomized, case/control trial in NH patients ≥ 80 years with a SBP<130 mmHg with >1 anti-Htn drugs. This trial will consist of two parallel arms: the intervention arm will entail antihypertensive drug step-down, while the control arm will comprise the standard anti-hypertensive treatment.

Detailed Description

High blood pressure (BP), principally systolic hypertension, is a common condition in older people and is considered a major determinant not only of cardiovascular morbidity and mortality, but also of several other age-related diseases, including frailty, cognitive decline and loss of autonomy. The Hypertension in the Very Elderly Treatment (HYVET) study showed the beneficial effect of antihypertensive treatment in patients ≥ 80 years. More recently, the Systolic Blood Pressure Intervention Trial (SPRINT) study showed that even in subjects 75 years and older, CVD outcomes and total mortality were reduced with intensive treatment as compared to the standard therapeutic strategies. However, both HYVET and SPRINT were conducted in selected populations since they excluded the most frail subjects, those with clinically significant cognitive decline and dementia, those with several cardiovascular and other co-morbidities, as well as patients living in medical-social institutions.

• Interestingly, observational studies in these frail people, have shown no or even an inverse relationship between BP and morbidity and mortality. The PARTAGE longitudinal study was performed in 1130 subjects ≥ 80 years living in medical-social institutions. These subjects were receiving at mean 7.1 drugs/day; 2/3 of them were under antihypertensive drugs (mean 2.2 drugs/day). The PARTAGE study showed an over-mortality in hypertensive subjects with low SBP (<130 mmHg) treated with 2 or more antihypertensive drugs. These individuals, who represented 20% of the total studied population, exhibited 80% increase in mortality compared to all other groups, even after adjustment for several comorbidities.
• The recent European guidelines for hypertension indicate that in people ≥ 80 years with SBP≥160 mmHg there is evidence to recommend reducing SBP to between 150 and 140 mmHg. However, no recommendation exists on which strategy to follow if treatment decreases SBP to lower levels (ex: 120 mmHg) especially on the more frail and polymedicated patients of that age. Thus, in this case, physicians can either continue the same treatment of reduce the number of drugs.
• These contrasting results in old hypertensives reflects the enormous functional heterogeneity among individual of this age-group and clearly show that functional status rather than chronological age should guide therapeutic strategies. Thus, the guidelines for robust older individuals cannot be extrapolated to very old, frail individuals, who have been completely excluded from the above-mentioned clinical trials.

The only way is to conduct a controlled clinical trial.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

1: Interventional (drug reduction)

STEP DOWN strategy.

Proposition of reduction of the number of antihypertensive medication according to:

• the systolic blood pressure levels,
• co-morbidities

Group Type: OTHER

STEP DOWN strategy

Intervention Type: OTHER

reduction of the number of antihypertensive medication according to:

• the systolic blood pressure levels,
• co-morbidities

2: Control

Usual treatment

Group Type: OTHER

Control

Intervention Type: OTHER

usual treatment

Interventions

STEP DOWN strategy

reduction of the number of antihypertensive medication according to:

• the systolic blood pressure levels,
• co-morbidities

Intervention Type: OTHER

Control

usual treatment

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Male and female patients aged 80 and over
• Patients living in nursing homes
• Patients with a SBP < 130 mmHg measured in Medical-Social Institutions using the connected blood pressure monitor supplied for the study (average of the last 2 out of 3 measurements after 10 min rest)
• Hypertensive patients whose treatment contains at least 2 antihypertensive molecules and whose treatment has been stabilised for at least :

• 3 weeks in the case of the introduction or discontinuation of an anti-HBP drug
• 2 weeks in the case of a change in the dosage of one of the anti-HBP drugs.
• Patients affiliated to a social security scheme
• Patients who have signed the informed consent form (failing which, the legal representative)
• Patients with dementia or with a severe reduction in physical function (impaired vision, asthenia, advanced osteoarthritis, severe tremors, etc.) and/or cognitive function may be included in this study with the agreement of their carers or family/relatives.

Exclusion Criteria

• Patients in whom no antihypertensive molecule can be reduced for specific reasons (heart failure with ejection fraction <40%, fluid retention due to heart failure, coronary artery disease and diabetic nephropathy).
• Patients with an estimated life expectancy of <3 months
• Patients who have already been included in this study or in another study at the same time

• Minimum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Athanase BENETOS, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHRU NANCY - Pôle Gérontologie

Locations

CHU Angoulême (Expert center)

Angoulême, , France

Font Douce (Nursing Home)

Angoulême, , France

Keriolet (Nursing Home)

Auray, , France

Kerleano (Nursing Home)

Auray, , France

Le Parc de la Plesse (Nursing Home)

Avrillé, , France

Sentiers d'Automne (Nursing Home)

Bains-les-Bains, , France

Parisot (Nursing Home)

Bainville-sur-Madon, , France

EHPAD du CH (Nursing Home)

Bar-sur-Seine, , France

EHPAD Fontarce (Nursing Home)

Bar-sur-Seine, , France

USLD du CH (Nursing Home)

Bar-sur-Seine, , France

Saint Charles (Nursing Home)

Bayon, , France

Argia (Nursing Home)

Bayonne, , France

EHPAD du Prisse (Nursing home)

Bayonne, , France

Goxoki (Nursing Home)

Bayonne, , France

EHPAD CH de Valence (Nursing home)

Beauvallon, , France

EHPAD Simone de Beauvoir (Nursing Home)

Béziers, , France

Espace Perréal (Nursing Home)

Béziers, , France

USLD Espace Perréal (Nursing Home)

Béziers, , France

CHU Bordeaux (Expert center)

Bordeaux, , France

La Croix Du Gue (Nursing Home)

Bouguenais, , France

Poincaré (Nursing Home)

Bouxières-aux-Dames, , France

Les Rives d'Ode (Nursing Home)

Carcassonne, , France

Les jardin de Sophia (Nursing Home)

Castelnau-le-Lez, , France

EHPAD de Monges (Nursing Home)

Castres, , France

La Villégiale Saint Jacques (Nursing Home)

Castres, , France

Saint Martin (Nursing Home)

Charmes, , France

Saint Jean (Nursing Home)

Charmois-l'Orgueilleux, , France

EHPAD CH Cotentin Pasteur (Nursing Home)

Cherbourg, , France

Centre pour Personnes Agées (Nursing Home)

Colmar, , France

Diaconnat (Nursing home)

Colmar, , France

Chantereine-Orpea (Nursing Home)

Coubron, , France

Le Hameau de Saubagnacq (Nursing Home)

Dax, , France

CHU Dijon (Expert center)

Dijon, , France

EHPAD CHU Dijon Bourgogne (Nursing Home)

Dijon, , France

Les Bégonias (Nursing Home)

Dijon, , France

Les marguerites (Nursing Home)

Dijon, , France

Port du Canal (Nursing Home)

Dijon, , France

EHPAD Simone Veil (Nursing Home)

Eaubonne, , France

Bas-Château (Nursing Home)

Essey-lès-Nancy, , France

Belfontaine (Nursing Home)

Fontaine-lès-Dijon, , France

Accueil Vologne (Nursing Home)

Granges-sur-Vologne, , France

Vallée Don (Nursing Home)

Guémené-Penfao, , France

EHPAD Orpéa (Nursing home)

La Talaudière, , France

Baudinet De Courcelles (Nursing home)

Lay-Saint-Christophe, , France

CHU Lille (Expert center)

Lille, , France

Les Bateliers (Nursing Home)

Lille, , France

Saint Antoine de Padoue (Nursing Home)

Lille, , France

EHPAD de Lormont (Nursing Home)

Lormont, , France

Sainte Thérèse (Nursing Home)

Ludres, , France

Saint Charles (Nursing Home)

Lunéville, , France

CHU Lyon (Expert center)

Lyon, , France

EHPAD Constant (Nursing Home)

Lyon, , France

La Renaissance-Orpea (Nursing Home)

Marseille, , France

Bon repos (Nursing Home)

Maxéville, , France

Saint Sauveur (Nursing Home)

Maxéville, , France

Félix Marechal (Nursing Home)

Metz, , France

USLD Nouvielle (Nursing Home)

Mont-de-Marsan, , France

Coteaux de Montmorency (Nursing Home)

Montmorency, , France

Jeanne Callarec (Nursing Home)

Montmorency, , France

Antonin Balmès (Nursing Home)

Montpellier, , France

CHU Montpellier (Expert center)

Montpellier, , France

CSPA Bellevue (Nursing Home)

Montpellier, , France

EHPAD du CH (Nursing Home)

Muret, , France

Les Cygnes (Nursing Home)

Nancy, , France

Notre Maison (Nursing home)

Nancy, , France

Saint Charles EHPAD (Nursing Home)

Nancy, , France

Saint Charles USLD (Nursing Home)

Nancy, , France

Saint Joseph (Nursing Home)

Nancy, , France

Saint Stanislas (Nursing Home)

Nancy, , France

Gériatrie - CHRU de Nancy (Expert center)

Nancy, , France

Beauséjour (Nursing Home)

Nantes, , France

CHU Nantes (Expert center)

Nantes, , France

La Chézalière LNA Santé (Nursing Home)

Nantes, , France

CHU Nice (Expert center)

Nice, , France

EHPAD Cimiez du CHU (Nursing Home)

Nice, , France

EHPAD GHAM (Nursing Home)

Nogent-sur-Seine, , France

Bethel (Nursing Home)

Oberhausbergen, , France

Les Jardins d'Olonne (Nursing Home)

Olonne-sur-Mer, , France

Résidence Mer et Estuaire (Nursing Home)

Paimboeuf, , France

APHP (Expert center)

Paris, , France

EHPAD Broca (Nursing Home)

Paris, , France

La Collégiale (Nursing Home)

Paris, , France

Saint Jacques Orpea (Nursing Home)

Paris, , France

Trocadéro-Orpéa (Nursing Home)

Paris, , France

USLD Pessac (Nursing Home)

Pessac, , France

CHU Périgueux (Expert center)

Périgueux, , France

EHPAD Parrot (Nursing Home)

Périgueux, , France

Avant-Garde (Nursing Home)

Pompey, , France

La Salle (Nursing Home)

Pompey, , France

Nazareth (Nursing Home)

Pont-Sainte-Marie, , France

Saint Jean (Nursing Home)

Portieux, , France

Jacques Mellez (Nursing Home)

Raon-l'Étape, , France

CHU Reims (Expert center)

Reims, , France

AHPAD AB2 Wilson (Nursing Home)

Reims, , France

Résidence Roux CHU Reims (Nursing Home)

Reims, , France

Julien Monnard (Nursing Home)

Romilly-sur-Seine, , France

Le Clos des platanes (Nursing Home)

Romilly-sur-Seine, , France

EHPAD Mer Et Pins (Nursing Home)

Saint-Brevin-les-Pins, , France

Mer et Pins Fleur d'Ajonc (Nursing Home)

Saint-Brevin-les-Pins, , France

Mer et Pins les Sylphes (Nursing Home)

Saint-Brevin-les-Pins, , France

Saint Deodat (Nursing Home)

Saint-Dié, , France

Fauriel (Nursing Home)

Saint-Etienne, , France

EHPAD de Saint Genest (Nursing Home)

Saint-Genest, , France

Udazkena (Nursing Home)

Saint-Jean-de-Luz, , France

Hotel Club (Nursing Home)

Saint-Max, , France

EHPAD De Senones (Nursing Home)

Senones, , France

EHPAD Sézanne (Nursing Home)

Sézanne, , France

CHU Strasbourg (Expert center)

Strasbourg, , France

EHPAD Bois Fleuri (Nursing Home)

Strasbourg, , France

EHPAD CHRU Robertsau (Nursing Home)

Strasbourg, , France

La Christinière ACPPA (Nursing Home)

Taluyers, , France

Sainte Sophie (Nursing Home)

Thiaucourt-Regniéville, , France

CHU Toulouse (Expert center)

Toulouse, , France

Jolimont Marengo Orpea (Nursing Home)

Toulouse, , France

Clinique les Minimes (Nursing Home)

Toulouse, , France

Klarene-Orpea (Nursing Home)

Tournan-en-Brie, , France

CHP Cotentin Simone Veil (Nursing Home)

Valognes, , France

EHPAD Maison du Lac (Nursing Home)

Vannes, , France

USLD Maison du Lac (Nursing Home)

Vannes, , France

Sainte Catherine (Nursing Home)

Verdun, , France

Saint Joseph (Nursing Home)

Ville-sur-Illon, , France

Montagne de Reims (Nursing home)

Villers-Allerand, , France

Villa Saint-Pierre (Nursing Home)

Villers-lès-Nancy, , France

Les Buissons (Nursing Home)

Xertigny, , France

Countries

France

References

Benetos A, Gautier S, Freminet A, Metz A, Labat C, Georgiopoulos I, Bertin-Hugault F, Beuscart JB, Hanon O, Karcher P, Manckoundia P, Novella JL, Diallo A, Vicaut E, Rossignol P; RETREAT-FRAIL Study Group. Reduction of Antihypertensive Treatment in Nursing Home Residents. N Engl J Med. 2025 Aug 29. doi: 10.1056/NEJMoa2508157. Online ahead of print.

Reference Type: DERIVED

PMID: 40879421 (View on PubMed)

Other Identifiers

2017-A01646-47

Identifier Type: OTHER

Identifier Source: secondary_id

P160602J

Identifier Type: -

Identifier Source: org_study_id