Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People
Primary Purpose
Hypertension, Systolic, Cerebrovascular Disease
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Anti-hypertensive therapy to SBP 130 mm Hg
Anti-hypertensive therapy to SBP 145 mm Hg
Sponsored by
About this trial
This is an interventional prevention trial for Hypertension, Systolic focused on measuring Hypertension, systolic, Elderly (> or equal to 75 years), Cerebrovascular disease
Eligibility Criteria
Inclusion Criteria:
- 75 years of age or older
- Seated clinic systolic BP >150 mmHg in the untreated state (see criterion D)
- At risk for cerebrovascular disease (history of smoking, dyslipidemia, type 2 diabetes, longstanding hypertension, family history). Patients must have visible (0.5% WMH or more)white-matter hypertensity lesions on screening magnetic resonance imaging
- To achieve success in maintaining a 24-hour systolic BP of <140-145 mmHg in the standard treatment group or a systolic BP <125-130 mmHg in the intensive treatment group, patients will be eligible for inclusion if (1) their clinic systolic BP is 150-170 mmHg, and they are taking 0 to 2 antihypertensives, (2) their systolic BP is >170 mmHg and they are taking 0 to 1 antihypertensives
Exclusion Criteria:
- Uncontrolled diabetes mellitus (HBA1c >10%)
- History of stroke, dementia or clinically impaired gait (Mini-mental status exam score (MMSE) <24, Short Physical Performance Battery for gait (SPPB) < 9,)
- Body Mass Index > 45 kg/m2 and/or arm circumference > 44 cm)
- Poor kidney function (defined as estimated GFR <30 ml/minute)
- Active liver disease or serum transaminases >3 times the upper limit of normal
- Major cardiovascular event (e.g. myocardial infarction) or procedure (e.g. cardiac bypass surgery) in past 3 months; stroke with residual gait abnormality
- Uncompensated congestive heart failure (NYHA class III or IV or documented ejection fraction <30%)
- Chronic atrial fibrillation that disallows ambulatory BP monitoring to be successfully performed
- Medical conditions that limit survival to < 3 years
- Non-dermatologic cancer diagnosed within 2 years
- Organ transplantation requiring anti-rejection drug therapy
- Severe and unexplained weight loss (>15%) in past 6 months
- Medical need to undergo recurrent phlebotomy or blood transfusions
- Current participation in another investigational trial
- Unable to obtain informed consent
- Factors limiting adherence to the interventions
- MRI contraindications (including MRI-incompatible implants, severe claustrophobia).
Sites / Locations
- University of Connecticut Health Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Intensive
Standard
Arm Description
Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg
Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg
Outcomes
Primary Outcome Measures
Mobility - Measured by Change in Gait Speed
Change in gait speed (walking 8 meters) in seconds mediated by the accrual of white-matter hyperintensity lesions (WMH/intracranial cavity volume) using MRI and including degeneration of axonal and myelin components of white matter using MRI technology known as diffusion tensor imaging (DTI).
Secondary Outcome Measures
Cognitive Function - as Measured by Change in Stroop Test Score
Change in cognitive function as measured by stroop test score: number of correct responses in 45 seconds.
The score for the Stroop Test is the number of correct responses provided in 45 seconds on each test condition: word reading, color naming, and inhibition. For the inhibition condition, words are written in an incongruous ink color (e.g., the word red written in blue ink) and participants must provide the ink color. Scores range from 0 to no upper limit, with higher scores indicating better performance.
Full Information
NCT ID
NCT01650402
First Posted
December 14, 2011
Last Updated
October 29, 2020
Sponsor
UConn Health
Collaborators
National Institute on Aging (NIA)
1. Study Identification
Unique Protocol Identification Number
NCT01650402
Brief Title
Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People
Official Title
Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
October 2018 (Actual)
Study Completion Date
October 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UConn Health
Collaborators
National Institute on Aging (NIA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This randomized clinical trial examines if lowering and maintaining 24-hour ambulatory systolic blood pressure to <130 mmHg (intensive control) versus <145 mmHg (standard control) slows/halts the progression of deterioration of mobility and cognitive function linked to white-matter disease (also known as white-matter hyperintensity or WMH) in patients with normal or mildly impaired mobility and cognition in subjects with detectable cerebrovascular disease (>0.5% WMH fraction of intracranial contents). The study patients will be enrolled and randomized to one of two levels of ambulatory blood pressure control (intensive to achieve a goal 24-hour systolic blood pressure of < 130 mmHg or standard to achieve a goal 24-hour systolic blood pressure of < 145 mmHg) for a total of 36 months.
Detailed Description
The study patients will be enrolled and randomized to one of two levels of ambulatory BP control (intensive to achieve a goal 24-hour systolic BP of < 130 mmHg or standard to achieve a goal 24-hour systolic BP of < 145 mmHg) for a total of 36 months. Similar antihypertensive regimens will be used in both of the treatment groups. Titration of antihypertensive therapies will be performed at monthly intervals for the first 3 to 6 months post-randomization to achieve goal systolic BP. The primary and secondary outcomes will be evaluated at baseline, and following 18 months and 36 months of therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Systolic, Cerebrovascular Disease
Keywords
Hypertension, systolic, Elderly (> or equal to 75 years), Cerebrovascular disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
199 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intensive
Arm Type
Experimental
Arm Description
Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg
Arm Title
Standard
Arm Type
Active Comparator
Arm Description
Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg
Intervention Type
Other
Intervention Name(s)
Anti-hypertensive therapy to SBP 130 mm Hg
Intervention Description
Anti-hypertensive therapy to achieve 24 hour systolic blood pressure less than or equal to 130 mm Hg
Intervention Type
Other
Intervention Name(s)
Anti-hypertensive therapy to SBP 145 mm Hg
Intervention Description
Anti-hypertensive therapy to achieve 24 hour systolic blood pressure less than or equal to 145 mm Hg
Primary Outcome Measure Information:
Title
Mobility - Measured by Change in Gait Speed
Description
Change in gait speed (walking 8 meters) in seconds mediated by the accrual of white-matter hyperintensity lesions (WMH/intracranial cavity volume) using MRI and including degeneration of axonal and myelin components of white matter using MRI technology known as diffusion tensor imaging (DTI).
Time Frame
Change from baseline to 36 months
Secondary Outcome Measure Information:
Title
Cognitive Function - as Measured by Change in Stroop Test Score
Description
Change in cognitive function as measured by stroop test score: number of correct responses in 45 seconds.
The score for the Stroop Test is the number of correct responses provided in 45 seconds on each test condition: word reading, color naming, and inhibition. For the inhibition condition, words are written in an incongruous ink color (e.g., the word red written in blue ink) and participants must provide the ink color. Scores range from 0 to no upper limit, with higher scores indicating better performance.
Time Frame
Change from baseline to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
75 years of age or older
Seated clinic systolic BP >150 mmHg in the untreated state (see criterion D)
At risk for cerebrovascular disease (history of smoking, dyslipidemia, type 2 diabetes, longstanding hypertension, family history). Patients must have visible (0.5% WMH or more)white-matter hypertensity lesions on screening magnetic resonance imaging
To achieve success in maintaining a 24-hour systolic BP of <140-145 mmHg in the standard treatment group or a systolic BP <125-130 mmHg in the intensive treatment group, patients will be eligible for inclusion if (1) their clinic systolic BP is 150-170 mmHg, and they are taking 0 to 2 antihypertensives, (2) their systolic BP is >170 mmHg and they are taking 0 to 1 antihypertensives
Exclusion Criteria:
Uncontrolled diabetes mellitus (HBA1c >10%)
History of stroke, dementia or clinically impaired gait (Mini-mental status exam score (MMSE) <24, Short Physical Performance Battery for gait (SPPB) < 9,)
Body Mass Index > 45 kg/m2 and/or arm circumference > 44 cm)
Poor kidney function (defined as estimated GFR <30 ml/minute)
Active liver disease or serum transaminases >3 times the upper limit of normal
Major cardiovascular event (e.g. myocardial infarction) or procedure (e.g. cardiac bypass surgery) in past 3 months; stroke with residual gait abnormality
Uncompensated congestive heart failure (NYHA class III or IV or documented ejection fraction <30%)
Chronic atrial fibrillation that disallows ambulatory BP monitoring to be successfully performed
Medical conditions that limit survival to < 3 years
Non-dermatologic cancer diagnosed within 2 years
Organ transplantation requiring anti-rejection drug therapy
Severe and unexplained weight loss (>15%) in past 6 months
Medical need to undergo recurrent phlebotomy or blood transfusions
Current participation in another investigational trial
Unable to obtain informed consent
Factors limiting adherence to the interventions
MRI contraindications (including MRI-incompatible implants, severe claustrophobia).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William B. White, M.D.
Organizational Affiliation
Pat and Jim Calhoun Cardiology Center, University of Connecticut Health Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Leslie Wolfson, M.D.
Organizational Affiliation
Department of Neurology, University of Connecticut Health Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Connecticut Health Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
36398903
Citation
Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2022 Nov 18;11(11):CD010315. doi: 10.1002/14651858.CD010315.pub5.
Results Reference
derived
PubMed Identifier
32905623
Citation
Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4.
Results Reference
derived
PubMed Identifier
31607143
Citation
White WB, Wakefield DB, Moscufo N, Guttmann CRG, Kaplan RF, Bohannon RW, Fellows D, Hall CB, Wolfson L. Effects of Intensive Versus Standard Ambulatory Blood Pressure Control on Cerebrovascular Outcomes in Older People (INFINITY). Circulation. 2019 Nov 12;140(20):1626-1635. doi: 10.1161/CIRCULATIONAHA.119.041603. Epub 2019 Oct 14.
Results Reference
derived
PubMed Identifier
30145340
Citation
White WB, Jalil F, Wakefield DB, Kaplan RF, Bohannon RW, Hall CB, Moscufo N, Fellows D, Guttmann CRG, Wolfson L. Relationships among clinic, home, and ambulatory blood pressures with small vessel disease of the brain and functional status in older people with hypertension. Am Heart J. 2018 Nov;205:21-30. doi: 10.1016/j.ahj.2018.08.002. Epub 2018 Aug 11.
Results Reference
derived
PubMed Identifier
23453090
Citation
White WB, Marfatia R, Schmidt J, Wakefield DB, Kaplan RF, Bohannon RW, Hall CB, Guttmann CR, Moscufo N, Fellows D, Wolfson L. INtensive versus standard ambulatory blood pressure lowering to prevent functional DeclINe in the ElderlY (INFINITY). Am Heart J. 2013 Mar;165(3):258-265.e1. doi: 10.1016/j.ahj.2012.11.008. Epub 2013 Jan 5.
Results Reference
derived
Learn more about this trial
Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People
We'll reach out to this number within 24 hrs