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Impact of the Reduction in Antihypertensive Treatment on Total Mortality in Frail Subjects With Low Systolic Blood Pressure: Study in Subjects Over 80 Years Living in Nursing Homes (RETREAT-FRAIL)

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ClinicalTrials.gov Identifier: NCT03453268
Recruitment Status : Recruiting
First Posted : March 5, 2018
Last Update Posted : September 15, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

The investigators hypothesize that a gradual reduction in antihypertensive treatment in nursing home (NH) 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.


Condition or disease Intervention/treatment Phase
Hypertension Other: STEP DOWN strategy Other: Control Not Applicable

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 nursing homes.

  • 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 nursing homes (NHs). 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Therapeutic strategies: reduction of the antihypertensive treatment (intervention arm) vs. usual treatment (control arm)
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Impact of the Reduction in Antihypertensive Treatment on Total Mortality in Frail Subjects With Low Systolic Blood Pressure: Randomized, Controlled Study in Subjects Over 80 Years Living in Nursing Homes
Actual Study Start Date : October 2, 2018
Estimated Primary Completion Date : October 1, 2022
Estimated Study Completion Date : October 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

2: Control
Usual treatment
Other: Control
usual treatment




Primary Outcome Measures :
  1. All-cause mortality [ Time Frame: up to 48 months ]
    during a follow up period of 24 months minimal to 48 months maximal


Secondary Outcome Measures :
  1. Blood pressure analysis [ Time Frame: up to 48 months ]
    Systolic BP, diastolic BP, pulse pressure (PP) in sitting position and then in upright position during the follow up period of 24-48 months

  2. Cause of deaths [ Time Frame: up to 48 months ]
    Major cardiovascular (CV) events (myocardial infarction, hospitalization for heart failure, stroke and any other serious CV complications requiring specific treatment or hospitalization) during the follow up period of 24-48 months

  3. Evaluation of frailty [ Time Frame: up to 48 months ]
    assessed by muscular force and Short Physical Performance Battery every 6 months

  4. Evaluation of autonomy [ Time Frame: up to 48 months ]
    assessed by scale Activites of Daily Living scale every 6 months

  5. Evaluation of cognitive function [ Time Frame: up to 48 months ]
    assessed by Mini Mental Status Evaluation (MMSE) every 6 months

  6. Number of falls [ Time Frame: up to 48 months ]
    Number of falls and recording of fractures during the follow up period of 24-48 months

  7. Medications [ Time Frame: up to 48 months ]
    Total number of medications, number of anti-hypertensive drugs during the follow up period of 24-48 months

  8. Evaluation of Quality of Life [ Time Frame: up to 48 months ]
    Indices of Quality of Life (EQ 5D) yearly



Information from the National Library of Medicine

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Ages Eligible for Study:   80 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient 80 years or older
  • Patient living in a NH
  • SBP <130 mmHg, as measured (with an electronic device with recorder) in nursing homes by nurses (average of 3 measurements after 10 min of rest). These SBP values should be recorded in the absence of any acute illness or condition inducing acute BP drop
  • Patient treated for hypertension with 2 or more antihypertensive drugs
  • Stable antihypertensive treatment (3 weeks for an introduction or stop and 2 weeks for a posology change)
  • Mandatory enrollment in a social security plan
  • Patient (or legal representative if applicable) having signed an informed consent.

Exclusion Criteria:

  • Patient in which none of antihypertensive drugs can be stopped because of simultaneous indications for other cardiovascular diseases.
  • Patient with estimated life expectancy <3 months.
  • Patient who has already been included in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03453268


Contacts
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Contact: Athanase BENETOS, MD, PhD +33-3-83-41-32-84 a.benetos@chru-nancy.fr
Contact: Sylvie GAUTIER, MD s.gautier@chru-nancy.fr

Locations
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France
Gériatrie - CHRU de Nancy Recruiting
Nancy, France, 54500
Contact: Sylvie GAUTIER-BENETOS, MD    0383153322    s.gautier@chru-nancy.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Athanase BENETOS, MD, PhD CHRU NANCY - Pôle Gérontologie
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03453268    
Other Study ID Numbers: P160602J
2017-A01646-47 ( Other Identifier: IDRCB )
First Posted: March 5, 2018    Key Record Dates
Last Update Posted: September 15, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Blood pressure
Aged
Frailty
Polypharmacy
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases