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

• Sponsor: UConn Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01650402
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 199
• Location: 1
• Arms: 2
• Duration (Months): 82
• Patients Per Site Per Month: 2.4

Study Details

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	N/A

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
• 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: Dec 1, 2011
• Actual Primary Completion Date: Oct 1, 2018
• Actual Study Completion Date: Oct 1, 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 [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 [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	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)

• Statistical Analysis Plan - Sep 25, 2018
• Study Protocol - Apr 16, 2018

More Information

Publications

None provided.

• Responsible Party: William B. White, Professor, UConn Health
• ClinicalTrials.gov Identifier: NCT01650402
• Other Study ID Numbers: 11-155S-2; 2R01AG022092-06A1
• First Posted: Jul 26, 2012
• Last Update Posted: Nov 18, 2020
• Last Verified: Oct 1, 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, Professor, UConn Health: Hypertension, systolic; Elderly (> or equal to 75 years); Cerebrovascular disease
• Additional relevant MeSH terms: Cerebrovascular Disorders; Hypertension; Systolic Murmurs; Antihypertensive Agents

Study Results

Participant Flow

Arm/Group Title	Intensive	Standard
Arm/Group Description	Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg 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	Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg 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
Period Title: Overall Study
STARTED	99	100
COMPLETED	79	86
NOT COMPLETED	20	14

Baseline Characteristics

Arm/Group Title	Intensive	Standard	Total
Arm/Group Description	Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg 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	Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg 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	Total of all reporting groups
Overall Participants	99	100	199
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	99 100%	100 100%	199 100%
Sex: Female, Male (Count of Participants)
Female	57 57.6%	51 51%	108 54.3%
Male	42 42.4%	49 49%	91 45.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2%	1 1%	3 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 7.1%	6 6%	13 6.5%
White	85 85.9%	89 89%	174 87.4%
More than one race	5 5.1%	4 4%	9 4.5%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

78 participants from the intensive group and 86 participants from the standard group were included in the mobility analysis because 1 participant from the intensive group did not complete mobility testing

Arm/Group Title	Intensive	Standard
Arm/Group Description	Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg 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	Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg 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
Measure Participants	78	86
Mean (Standard Deviation) [seconds]	0.4 (2.0)	0.42 (2.73)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

69 participants from the intensive group and 76 participants from the standard group were included in analysis because 10 participants in the intensive group and 10 participants in the standard group did not complete cognitive testing

Arm/Group Title	Intensive	Standard
Arm/Group Description	Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg 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	Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg 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
Measure Participants	69	76
Mean (Standard Deviation) [correct responses]	-2.7 (8.0)	-0.8 (6.4)

Adverse Events

Time Frame	Adverse event data were collected throughout a participant's study completion, an average of 36 months
Arm/Group Title	Intensive		Standard
Arm/Group Description	Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg 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		Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg 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
All Cause Mortality
	Intensive		Standard
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/99 (2%)		4/100 (4%)
Serious Adverse Events
	Intensive		Standard
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/99 (33.3%)		36/100 (36%)
Blood and lymphatic system disorders
Anemia	3/99 (3%)	3	0/100 (0%)	0
Cardiac disorders
Arrhythmia	3/99 (3%)	3	4/100 (4%)	4
Heart failure	0/99 (0%)	0	2/100 (2%)	2
Stroke	2/99 (2%)	2	2/100 (2%)	2
Myocardial infarction	0/99 (0%)	0	4/100 (4%)	4
Pacemaker implantation	1/99 (1%)	1	2/100 (2%)	2
Presyncope	3/99 (3%)	4	2/100 (2%)	2
Heart stent placement	0/99 (0%)	0	1/100 (1%)	1
Other cardiac hospitalizations	1/99 (1%)	2	2/100 (2%)	2
Endocrine disorders
Hyperglycemia hospitalization	0/99 (0%)	0	1/100 (1%)	1
Pancreatic cancer diagnosis	1/99 (1%)	1	0/100 (0%)	0
Gastrointestinal disorders
Bowel obstruction	2/99 (2%)	2	2/100 (2%)	5
Gastrointestinal bleed	2/99 (2%)	3	1/100 (1%)	1
Cholecystectomy	1/99 (1%)	1	1/100 (1%)	1
Diarrhea	0/99 (0%)	0	1/100 (1%)	1
Colon cancer diagnosis	0/99 (0%)	0	1/100 (1%)	1
General disorders
Hospitalization for fall	3/99 (3%)	3	2/100 (2%)	2
Hospitalization for pain	2/99 (2%)	2	1/100 (1%)	1
Hospitalization for fatigue	0/99 (0%)	0	1/100 (1%)	1
Hospitalization for weakness	1/99 (1%)	1	0/100 (0%)	0
Death due to cancer	1/99 (1%)	1	1/100 (1%)	1
Infections and infestations
Sepsis	0/99 (0%)	0	1/100 (1%)	1
Influenza	2/99 (2%)	2	0/100 (0%)	0
Bronchitis	1/99 (1%)	1	0/100 (0%)	0
Pneumonia	2/99 (2%)	2	2/100 (2%)	3
Upper respiratory infection	0/99 (0%)	0	1/100 (1%)	1
Musculoskeletal and connective tissue disorders
Gout	1/99 (1%)	1	0/100 (0%)	0
Nervous system disorders
Aphasia	0/99 (0%)	0	2/100 (2%)	2
Vertigo	0/99 (0%)	0	1/100 (1%)	1
Renal and urinary disorders
Urinary tract infection	1/99 (1%)	1	1/100 (1%)	1
Urinary retention	1/99 (1%)	1	0/100 (0%)	0
Reproductive system and breast disorders
Breast cancer diagnosis	0/99 (0%)	0	1/100 (1%)	1
Respiratory, thoracic and mediastinal disorders
COPD exacerbation	0/99 (0%)	0	1/100 (1%)	8
Surgical and medical procedures
Hip surgery	3/99 (3%)	3	4/100 (4%)	5
Knee surgery	4/99 (4%)	5	0/100 (0%)	0
Abdominoplasty	0/99 (0%)	0	1/100 (1%)	1
Hernia repair	1/99 (1%)	1	1/100 (1%)	1
Ovarian mass removal	1/99 (1%)	1	0/100 (0%)	0
Back surgery	2/99 (2%)	2	0/100 (0%)	0
Leg amputation	0/99 (0%)	0	1/100 (1%)	1
Thyroid surgery	1/99 (1%)	1	1/100 (1%)	1
Pump placed for incontinence	1/99 (1%)	1	0/100 (0%)	0
Vascular disorders
Pulmonary Emboli	0/99 (0%)	0	1/100 (1%)	1
Subdural hematoma	1/99 (1%)	1	1/100 (1%)	1
Other (Not Including Serious) Adverse Events
	Intensive		Standard
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/99 (86.9%)		70/100 (70%)
General disorders
Fatigue	5/99 (5.1%)	5	5/100 (5%)	6
Fall	30/99 (30.3%)	40	31/100 (31%)	44
Nervous system disorders
Dizziness	9/99 (9.1%)	11	6/100 (6%)	7
Lightheadedness	12/99 (12.1%)	16	6/100 (6%)	8
Renal and urinary disorders
Urinary Tract Infection	8/99 (8.1%)	10	9/100 (9%)	12
Vascular disorders
Edema	22/99 (22.2%)	22	13/100 (13%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.