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

UConn Health

Status: Completed

Conditions: Cerebrovascular Disease; Hypertension, Systolic

Treatments: Other: Anti-hypertensive therapy to SBP 130 mm Hg; Other: Anti-hypertensive therapy to SBP 145 mm Hg

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01650402

2R01AG022092-06A1 (U.S. NIH Grant/Contract)

11-155S-2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 199 patients

Sex: All

Ages: 75+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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199 participants in 2 patient groups

Intensive

Experimental 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

Treatment:

Other: Anti-hypertensive therapy to SBP 130 mm Hg

Standard

Active Comparator group

Description:

Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg

Treatment:

Other: Anti-hypertensive therapy to SBP 145 mm Hg