Systolic Blood Pressure Intervention Trial

Study Overview
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Brief Summary
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Elevated blood pressure (BP) is an important public health concern. It is highly prevalent, the prevalence may be increasing, and it is a risk factor for several adverse health outcomes, especially coronary heart disease, stroke, heart failure, chronic kidney disease, and decline in cognitive function. The Systolic Blood Pressure Intervention Trial (SPRINT) is a 2-arm, multicenter, randomized clinical trial designed to test whether a treatment program aimed at reducing systolic blood pressure (SBP) to a lower goal than currently recommended will reduce cardiovascular disease (CVD) risk.

Detailed Description
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SPRINT strived to enroll about 9250 participants aged ≥ 50 years with SBP ≥130 mm Hg and at least one additional CVD risk factor. The trial compared the effects of randomization to a treatment program of an intensive SBP goal with randomization to a treatment program of a standard goal. Target SBP goals were <120 vs <140 mm Hg, respectively, to create a minimum mean difference of 10 mm Hg between the two randomized groups. The primary hypothesis was that CVD event rates would be lower in the intensive arm. Participants were recruited at approximately 90 clinics within 5 clinical center networks (CCNs) over approximately a 2-year period, and were followed for 4-6 years. A total of 9361 participants were enrolled. NIH stopped the blood pressure intervention earlier than originally planned in order to quickly disseminate the significant preliminary results. Follow-up for cognitive and kidney outcomes continues during the post-intervention phase through May 2018.

Official Title
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Systolic Blood Pressure Intervention Trial

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Intensive control of SBP
* Drug: Standard control of SBP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 50 years old Systolic blood pressure of 130 - 180 mm Hg on 0 or 1 medication 130 - 170 mm Hg on up to 2 medications 130 - 160 mm Hg on up to 3 medications 130 - 150 mm Hg on up to 4 medications Risk (one or more of the following) Presence of clinical or subclinical cardiovascular disease other than stroke CKD, defined as eGFR 20 - 59 ml/min/1.73m2 A Framingham Risk Score for 10-year CVD risk ≥ 15% Age greater than 75 years Exclusion Criteria: An indication for a specific BP lowering medication that the person is not taking and the person has not been documented to be intolerant of the medication class. Known secondary cause of hypertension that causes concern regarding safety of the protocol. One minute standing SBP < 110 mm Hg. Proteinuria in the following ranges (based on a measurement within the past 6 months) 24 hour urinary protein excretion ≥1 g/day, or 24 hour urinary albumin excretion ≥ 600 mg/day, or spot urine protein/creatinine ratio ≥ 1 g/g creatinine, or spot urine albumin/creatinine ratio ≥ 600 mg/g creatinine, or urine dipstick ≥ 2+ protein Arm circumference too large or small to allow accurate blood pressure measurement with available devices Diabetes mellitus, History of stroke (not CE or stenting) Diagnosis of polycystic kidney disease Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy eGFR < 20 ml/min /1.73m2 or end-stage renal disease (ESRD) Cardiovascular event or procedure (as defined above as clinical CVD for study entry) or hospitalization for unstable angina within last 3 months Symptomatic heart failure within the past 6 months or left ventricular ejection fraction (by any method) < 35% A medical condition likely to limit survival to less than 3 years or a malignancy other than non-melanoma skin cancer within the last 2 years Any factors judged by the clinic team to be likely to limit adherence to interventions. Failure to obtain informed consent from participant Currently participating in another clinical trial (intervention study). Note: Patient must wait until the completion of his/her activities or the completion of the other trial before being screened for SPRINT. Living in the same household as an already randomized SPRINT participant Any organ transplant Unintentional weight loss > 10% in last 6 months Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive Control of SBP<br>Participants randomized into the Intensive BP arm will have a goal of SBP <120 mm Hg. 2-drug therapy initiated in most Intensive participants; age ≥75 years and SBP 130-139 mm Hg on 0-1 drug; may begin with 1 drug, but add second at 1 month if SBP ≥130 mm Hg; drugs added and/or titrated at each visit (monthly) to achieve SBP <120 mm Hg; at periodic milepost visits: addition of another drug required if not at goal. | Drug: Intensive control of SBP<br>* Participants in the Intensive arm have a goal of SBP <120 mm Hg. Use of once-daily antihypertensive agents will be encouraged unless alternative frequency is indicated/necessary. One or more medications from the following classes of agents will be provided by the study for use in managing participants in both randomization groups to achieve study goals: Angiotension converting enzyme (ACE)-inhibitors Angiotension receptor blockers (ARBs) Direct vasodilators Thiazide-type diuretics Loop diuretics Potassium-sparing diuretics Beta-blockers Sustained-release calcium channel blockers (CCBs) Alpha1-receptor blockers Sympatholytics Combination products will be available, depending on cost, utility, or donations from pharmaceutical companies.<br>* Other names: Comparison of standard SBP control to a target of 120 mm Hg;|
| Active Comparator: Standard Control of SBP<br>Participants randomized into the Standard arm will have a goal of SBP <140 mm Hg. Intensify therapy if SBP ≥160 mm Hg @ 1 visit; ≥140 mm Hg @ 2 consecutive visits; Down-titration if SBP <130 mm Hg @ 1 visit; <135 mm Hg @ 2 consecutive visits | Drug: Standard control of SBP<br>* Participants in the Standard BP arm have a goal of SBP <140 mm Hg. The same medications used in the Intensive BP arm will be used for the Standard BP arm.<br>* Other names: Control of SBP to a target of 140 mm Hg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With First Occurrence of a Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Stroke, Heart Failure (HF), or CVD Death |  | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With All-cause Mortality |  | 6 years | 
| Number of CKD Participants Who Experienced a 50% Decline From Baseline eGFR |  | 6 years | 
| Participants Who Developed End Stage Renal Disease |  | 6 years | 
| Number of Patients With All-cause Dementia | A 3-step process was used ascertain incident cases of all-cause dementia. First, to identify possible cases of dementia a brief Cognition Screening Battery was administered to all participants. Participants who score below the pre-designated screening cut-point for possible cognitive impairment during follow-up were administered a more comprehensive and detailed neurocognitive test battery (the Extended Cognitive Assessment Battery) plus the Functional Assessment Questionnaire (FAQ) which assesses impairments in daily living skills as a result of cognitive impairments. Last, all the above available tests and questionnaire data were submitted to a centralized, web-based system for adjudication by a panel of dementia experts who assigned final study classifications of probable dementia (PD), mild cognitive impairment (MCI) or no impairment (NI). | 6 years | 
| Small Vessel Cerebral Ischemic Disease | Change over 4 years in total white matter lesion volume from baseline Change over 4 years in total brain volume from baseline Because of the skewed distribution for WML volume, we first applied an inverse hyperbolic sine transformation (asinh), which is similar to a log transformation but can accommodate values of zero. Linear mixed models, including random effects for participant and MRI facility, were used to estimate the change in WML volume and TBV between the treatment groups, including time since randomization (in days) and intracranial volume as covariates. Because the inverse hyperbolic sine transformation is nonlinear, and given the context of a mixed-effects model, back-transformation to the original scale of cm3 is difficult | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood pressure, antihypertensive, systolic, diastolic, heart failure, myocardial infarction, stroke, chronic kidney disease, dementia, cognitive decline