Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People

• ClinicalTrials.gov Identifier: NCT01650402
• Recruitment Status: Completed
• First Posted: July 26, 2012
• Results First Posted: October 30, 2020
• Last Update Posted: November 18, 2020
• Sponsor: UConn Health
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): William B. White, UConn Health

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.

Condition or disease	Intervention/treatment	Phase
Hypertension, Systolic; Cerebrovascular Disease	Other: Anti-hypertensive therapy to SBP 130 mm Hg; Other: Anti-hypertensive therapy to SBP 145 mm Hg	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 199 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People
• Study Start Date: December 2011
• Actual Primary Completion Date: October 2018
• Actual Study Completion Date: October 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intensive; Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg	Other: Anti-hypertensive therapy to SBP 130 mm Hg; Anti-hypertensive therapy to achieve 24 hour systolic blood pressure less than or equal to 130 mm Hg
Active Comparator: Standard; Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg	Other: Anti-hypertensive therapy to SBP 145 mm Hg; Anti-hypertensive therapy to achieve 24 hour systolic blood pressure less than or equal to 145 mm Hg

Outcome Measures

Primary Outcome Measures :

1. Mobility - Measured by Change in Gait Speed [ Time Frame: Change from baseline to 36 months ]
   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 :

1. Cognitive Function - as Measured by Change in Stroop Test Score [ Time Frame: Change from baseline to 36 months ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 75 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

United States, Connecticut

University of Connecticut Health Center

Farmington, Connecticut, United States, 06030

Sponsors and Collaborators

UConn Health

National Institute on Aging (NIA)

Investigators

• Principal Investigator: William B. White, M.D.; Pat and Jim Calhoun Cardiology Center, University of Connecticut Health Center
• Principal Investigator: Leslie Wolfson, M.D.; Department of Neurology, University of Connecticut Health Center

  Study Documents (Full-Text)

Documents provided by William B. White, UConn Health:

Statistical Analysis Plan  [PDF] September 25, 2018

Study Protocol  [PDF] April 16, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

• Responsible Party: William B. White, Professor, UConn Health
• ClinicalTrials.gov Identifier: NCT01650402
• Other Study ID Numbers: 11-155S-2; 2R01AG022092-06A1 ( U.S. NIH Grant/Contract )
• First Posted: July 26, 2012
• Results First Posted: October 30, 2020
• Last Update Posted: November 18, 2020
• Last Verified: October 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by William B. White, UConn Health:

Hypertension, systolic; Elderly (> or equal to 75 years); Cerebrovascular disease

Additional relevant MeSH terms:

Cerebrovascular Disorders; Hypertension; Systolic Murmurs; Vascular Diseases; Cardiovascular Diseases; Heart Murmurs; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Antihypertensive Agents