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

July 16, 2025 updated by: Assistance Publique - Hôpitaux de Paris

Impact of Reducing Antihypertensive Treatment on Mortality in Frail Subjects With Low Systolic Blood Pressure (SBP). Multicenter, Randomized Controlled Study of Subjects Aged 80 and Over, Living in Nursing Homes and Other IMS.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1048

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angoulême, France, 16000
        • CHU Angoulême (Expert center)
      • Angoulême, France, 16000
        • Font Douce (Nursing Home)
      • Auray, France, 56400
        • Keriolet (Nursing Home)
      • Auray, France, 56400
        • Kerleano (Nursing Home)
      • Avrillé, France, 49240
        • Le Parc de la Plesse (Nursing Home)
      • Bains-les-Bains, France, 88240
        • Sentiers d'Automne (Nursing Home)
      • Bainville sur Madon, France, 54550
        • Parisot (Nursing Home)
      • Bar-sur-Seine, France, 10110
        • EHPAD du CH (Nursing Home)
      • Bar-sur-Seine, France, 10110
        • EHPAD Fontarce (Nursing Home)
      • Bar-sur-Seine, France, 10110
        • USLD du CH (Nursing Home)
      • Bayon, France, 54290
        • Saint Charles (Nursing Home)
      • Bayonne, France, 64100
        • Argia (Nursing Home)
      • Bayonne, France, 64100
        • EHPAD du Prisse (Nursing home)
      • Bayonne, France, 64100
        • Goxoki (Nursing Home)
      • Beauvallon, France, 26800
        • EHPAD CH de Valence (Nursing home)
      • Bordeaux, France, 33000
        • CHU Bordeaux (Expert center)
      • Bouguenais, France, 44340
        • La Croix Du Gue (Nursing Home)
      • Bouxières-aux-Dames, France, 54136
        • Poincaré (Nursing Home)
      • Béziers, France, 34500
        • EHPAD Simone de Beauvoir (Nursing Home)
      • Béziers, France, 34500
        • Espace Perréal (Nursing Home)
      • Béziers, France, 34500
        • USLD Espace Perréal (Nursing Home)
      • Carcassonne, France, 11000
        • Les Rives d'Ode (Nursing Home)
      • Castelnau-le-Lez, France, 34057
        • Les jardin de Sophia (Nursing Home)
      • Castres, France, 81090
        • EHPAD de Monges (Nursing Home)
      • Castres, France, 81090
        • La Villégiale Saint Jacques (Nursing Home)
      • Charmes, France, 88130
        • Saint Martin (Nursing Home)
      • Charmois-l'Orgueilleux, France, 88270
        • Saint Jean (Nursing Home)
      • Cherbourg, France, 50100
        • EHPAD CH Cotentin Pasteur (Nursing Home)
      • Colmar, France, 68000
        • Centre pour Personnes Agées (Nursing Home)
      • Colmar, France, 68000
        • Diaconnat (Nursing home)
      • Coubron, France, 93470
        • Chantereine-Orpea (Nursing Home)
      • Dax, France, 40088
        • Le Hameau de Saubagnacq (Nursing Home)
      • Dijon, France, 21000
        • CHU Dijon (Expert center)
      • Dijon, France, 21000
        • EHPAD CHU Dijon Bourgogne (Nursing Home)
      • Dijon, France, 21000
        • Les Bégonias (Nursing Home)
      • Dijon, France, 21000
        • Les marguerites (Nursing Home)
      • Dijon, France, 21000
        • Port du Canal (Nursing Home)
      • Eaubonne, France, 95600
        • EHPAD Simone Veil (Nursing Home)
      • Essey-lès-Nancy, France, 54270
        • Bas-Château (Nursing Home)
      • Fontaine-lès-Dijon, France, 21121
        • Belfontaine (Nursing Home)
      • Granges-sur-Vologne, France, 88640
        • Accueil Vologne (Nursing Home)
      • Guémené penfao, France, 44290
        • Vallée Don (Nursing Home)
      • La Talaudière, France, 42350
        • EHPAD Orpéa (Nursing home)
      • Lay-Saint-Christophe, France, 54690
        • Baudinet De Courcelles (Nursing home)
      • Lille, France, 59000
        • CHU Lille (Expert center)
      • Lille, France, 59000
        • Les Bateliers (Nursing Home)
      • Lille, France, 59000
        • Saint Antoine de Padoue (Nursing Home)
      • Lormont, France, 33310
        • EHPAD de Lormont (Nursing Home)
      • Ludres, France, 54710
        • Sainte Thérèse (Nursing Home)
      • Lunéville, France, 54300
        • Saint Charles (Nursing Home)
      • Lyon, France, 69000
        • CHU Lyon (Expert center)
      • Lyon, France, 69000
        • EHPAD Constant (Nursing Home)
      • Marseille, France, 13000
        • La Renaissance-Orpea (Nursing Home)
      • Maxéville, France, 54320
        • Bon repos (Nursing Home)
      • Maxéville, France, 54320
        • Saint Sauveur (Nursing Home)
      • Metz, France, 57000
        • Félix Marechal (Nursing Home)
      • Mont-de-Marsan, France, 40192
        • USLD Nouvielle (Nursing Home)
      • Montmorency, France, 78428
        • Coteaux de Montmorency (Nursing Home)
      • Montmorency, France, 78428
        • Jeanne Callarec (Nursing Home)
      • Montpellier, France, 34000
        • Antonin Balmès (Nursing Home)
      • Montpellier, France, 34000
        • CHU Montpellier (Expert center)
      • Montpellier, France, 34000
        • CSPA Bellevue (Nursing Home)
      • Muret, France, 31600
        • EHPAD du CH (Nursing Home)
      • Nancy, France, 54000
        • Les Cygnes (Nursing Home)
      • Nancy, France, 54000
        • Notre Maison (Nursing home)
      • Nancy, France, 54000
        • Saint Charles EHPAD (Nursing Home)
      • Nancy, France, 54000
        • Saint Charles USLD (Nursing Home)
      • Nancy, France, 54000
        • Saint Joseph (Nursing Home)
      • Nancy, France, 54000
        • Saint Stanislas (Nursing Home)
      • Nancy, France, 54500
        • Gériatrie - CHRU de Nancy (Expert center)
      • Nantes, France, 44000
        • Beauséjour (Nursing Home)
      • Nantes, France, 44000
        • CHU Nantes (Expert center)
      • Nantes, France, 44000
        • La Chézalière LNA Santé (Nursing Home)
      • Nice, France, 06000
        • CHU Nice (Expert center)
      • Nice, France, 06000
        • EHPAD Cimiez du CHU (Nursing Home)
      • Nogent-sur-Seine, France, 10400
        • EHPAD GHAM (Nursing Home)
      • Oberhausbergen, France, 67205
        • Bethel (Nursing Home)
      • Olonne-sur-Mer, France, 85340
        • Les Jardins d'Olonne (Nursing Home)
      • Paimboeuf, France, 44560
        • Résidence Mer et Estuaire (Nursing Home)
      • Paris, France, 75000
        • APHP (Expert center)
      • Paris, France, 75013
        • EHPAD Broca (Nursing Home)
      • Paris, France, 75013
        • La Collégiale (Nursing Home)
      • Paris, France, 75013
        • Saint Jacques Orpea (Nursing Home)
      • Paris, France, 75016
        • Trocadéro-Orpéa (Nursing Home)
      • Pessac, France, 33318
        • USLD Pessac (Nursing Home)
      • Pompey, France, 54340
        • Avant-Garde (Nursing Home)
      • Pompey, France, 54340
        • La Salle (Nursing Home)
      • Pont-Sainte-Marie, France, 10150
        • Nazareth (Nursing Home)
      • Portieux, France, 88330
        • Saint Jean (Nursing Home)
      • Périgueux, France, 24000
        • CHU Périgueux (Expert center)
      • Périgueux, France, 24000
        • EHPAD Parrot (Nursing Home)
      • Raon-l'Étape, France, 88110
        • Jacques Mellez (Nursing Home)
      • Reims, France, 51100
        • CHU Reims (Expert center)
      • Reims, France, 51454
        • AHPAD AB2 Wilson (Nursing Home)
      • Reims, France, 51454
        • Résidence Roux CHU Reims (Nursing Home)
      • Romilly sur Seine, France, 10100
        • Le Clos des platanes (Nursing Home)
      • Romilly-sur-Seine, France, 10100
        • Julien Monnard (Nursing Home)
      • Saint-Brevin-les-Pins, France, 44250
        • EHPAD Mer Et Pins (Nursing Home)
      • Saint-Brevin-les-Pins, France, 44250
        • Mer et Pins Fleur d'Ajonc (Nursing Home)
      • Saint-Brevin-les-Pins, France, 44250
        • Mer et Pins les Sylphes (Nursing Home)
      • Saint-Dié-des-Vosges, France, 88100
        • Saint Deodat (Nursing Home)
      • Saint-Genest, France, 88700
        • EHPAD de Saint Genest (Nursing Home)
      • Saint-Jean-de-Luz, France, 64500
        • Udazkena (Nursing Home)
      • Saint-Max, France, 54130
        • Hotel Club (Nursing Home)
      • Saint-Étienne, France, 42000
        • Fauriel (Nursing Home)
      • Senones, France, 88210
        • EHPAD De Senones (Nursing Home)
      • Strasbourg, France, 67000
        • CHU Strasbourg (Expert center)
      • Strasbourg, France, 67000
        • EHPAD Bois Fleuri (Nursing Home)
      • Strasbourg, France, 67000
        • EHPAD CHRU Robertsau (Nursing Home)
      • Sézanne, France, 51120
        • EHPAD Sézanne (Nursing Home)
      • Taluyers, France, 69440
        • La Christinière ACPPA (Nursing Home)
      • Thiaucourt-Regniéville, France, 54470
        • Sainte Sophie (Nursing Home)
      • Toulouse, France, 31000
        • CHU Toulouse (Expert center)
      • Toulouse, France, 31000
        • Jolimont Marengo Orpea (Nursing Home)
      • Toulouse, France, 31200
        • Clinique les Minimes (Nursing Home)
      • Tournan-en-Brie, France, 77220
        • Klarene-Orpea (Nursing Home)
      • Valognes, France, 50700
        • CHP Cotentin Simone Veil (Nursing Home)
      • Vannes, France, 56000
        • EHPAD Maison du Lac (Nursing Home)
      • Vannes, France, 56000
        • USLD Maison du Lac (Nursing Home)
      • Verdun, France, 55100
        • Sainte Catherine (Nursing Home)
      • Ville-sur-Illon, France, 88270
        • Saint Joseph (Nursing Home)
      • Villers-Allerand, France, 51500
        • Montagne de Reims (Nursing home)
      • Villers-lès-Nancy, France, 54600
        • Villa Saint-Pierre (Nursing Home)
      • Xertigny, France, 88220
        • Les Buissons (Nursing Home)

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

80 years and older (Older Adult)

Accepts Healthy Volunteers

No

Description

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

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: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: 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
Other: STEP DOWN strategy

reduction of the number of antihypertensive medication according to:

  • the systolic blood pressure levels,
  • co-morbidities
Other: 2: Control
Usual treatment
Other: Control
usual treatment

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
All-cause mortality
Time Frame: up to 48 months
All-cause mortality in each of the two groups during follow-up (maximum 48 months depending on when the patient was included).
up to 48 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cause of death
Time Frame: up to 48 months
Occurrence of major CV events (myocardial infarction, hospitalisation for heart failure, stroke, other serious CV complication requiring specific management or hospitalisation)
up to 48 months
Blood pressure analysis
Time Frame: up to 48 months
SBP, diastolic blood pressure (DBP), pulse pressure (PP) and heart rate (HR) in the sitting position (or supine if sitting is not possible) and standing position (if possible), during the 24 to 48 month follow-up period.s
up to 48 months
Evaluation of frailty
Time Frame: up to 48 months
Frailty tests: weight, muscle strength (handgrip), Short Physical Performance Battery (SPPB) and assessment of independence using the ADL (Activities of Daily Living) scale every 6 months during the follow-up period at medical visits.
up to 48 months
Evaluation of cognitive function
Time Frame: up to 48 months
Assessment of cognitive functions by MMSE (Mini Mental State Evaluation) every six months during the follow-up period at medical visits.
up to 48 months
Assesment of fall and fractures
Time Frame: up to 48 months
Number of falls and fractures
up to 48 months
Medication assessment
Time Frame: up to 48 months
Total number of medications: number of antihypertensive medications during the 24 to 48 month follow-up period.
up to 48 months
Evaluation of Quality of life
Time Frame: up to 48 months
Quality of life scales (EQ 5D) once a year during the follow-up period at medical visits.
up to 48 months
Onset of cardiac decompensation
Time Frame: up to 48 months
Occurrence of cardiac decompensation, whether fatal or not, and monitoring of changes in blood pressure.
up to 48 months
Patient at high risk of decompensation
Time Frame: up to 48 months
Number of patients at high risk of cardiac decompensation.
up to 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Athanase BENETOS, MD, PhD, CHRU NANCY - Pôle Gérontologie

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 2, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 15, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 15, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 31, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 5, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 20, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P160602J
  • 2017-A01646-47 (Other Identifier: IDRCB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on Hypertension

Clinical Trials on STEP DOWN strategy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings