SPRINT: Systolic Blood Pressure Intervention Trial

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01206062
• Collaborator: National Institute on Aging (NIA) (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Wake Forest University Health Sciences (Other)
• Enrollment: 9,361
• Location: 1
• Arms: 2
• Actual Duration (Months): 101
• Patients Per Site Per Month: 92.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Intensive control of SBP; Drug: Standard control of SBP	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9361 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Systolic Blood Pressure Intervention Trial
• Actual Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intensive Control of SBP 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; 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.; Other Names: Lower target for SBP Comparison of standard SBP control to a target of 120 mm Hg
Active Comparator: Standard Control of SBP 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; 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.; Other Names: Control of SBP to a target of 140 mm Hg

Outcome Measures

Primary Outcome Measures

1. 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

1. Number of Participants With All-cause Mortality [6 years]

2. Number of CKD Participants Who Experienced a 50% Decline From Baseline eGFR [6 years]

3. Participants Who Developed End Stage Renal Disease [6 years]

4. Number of Patients With All-cause Dementia [6 years]

   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).

5. Small Vessel Cerebral Ischemic Disease [4 years]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

1. Presence of clinical or subclinical cardiovascular disease other than stroke

2. CKD, defined as eGFR 20 - 59 ml/min/1.73m2

3. A Framingham Risk Score for 10-year CVD risk ≥ 15%

4. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• National Institute on Aging (NIA)
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• National Institute of Neurological Disorders and Stroke (NINDS)
• Wake Forest University Health Sciences

Investigators

• Principal Investigator: David M. Reboussin, PhD, Wake Forest University Health Sciences
• Principal Investigator: Jackson T Wright, MD, Case Western Reserve University
• Principal Investigator: Alfred Cheung, MD, University of Utah
• Principal Investigator: Suzanne Oparil, MD, University of Alabama at Birmingham
• Principal Investigator: Mike Rocco, MD, Wake Forest University Health Sciences
• Principal Investigator: Bill Cushman, MD, Memphis VA Medical Center

Study Documents (Full-Text)

• Study Protocol - Nov 1, 2012
• Informed Consent Form - Jun 10, 2011

More Information

Publications

• Ambrosius WT, Sink KM, Foy CG, Berlowitz DR, Cheung AK, Cushman WC, Fine LJ, Goff DC Jr, Johnson KC, Killeen AA, Lewis CE, Oparil S, Reboussin DM, Rocco MV, Snyder JK, Williamson JD, Wright JT Jr, Whelton PK; SPRINT Study Research Group. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials. 2014 Oct;11(5):532-46. doi: 10.1177/1740774514537404. Epub 2014 Jun 5. Erratum in: Clin Trials. 2017 Apr;14(2):222.
• Ramsey TM, Snyder JK, Lovato LC, Roumie CL, Glasser SP, Cosgrove NM, Olney CM, Tang RH, Johnson KC, Still CH, Gren LH, Childs JC, Crago OL, Summerson JH, Walsh SM, Perdue LH, Bankowski DM, Goff DC; SPRINT Study Research Group. Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial. Clin Trials. 2016 Jun;13(3):319-30. doi: 10.1177/1740774516631735. Epub 2016 Feb 24.

• Responsible Party: David Reboussin, Principal Investigator, Coordinating Center, Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01206062
• Other Study ID Numbers: SPRINT; 268200900040C-1-0-1
• First Posted: Sep 21, 2010
• Last Update Posted: Jan 8, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by David Reboussin, Principal Investigator, Coordinating Center, Wake Forest University Health Sciences: blood pressure; antihypertensive; systolic; diastolic; heart failure; myocardial infarction; stroke; chronic kidney disease; dementia; cognitive decline
• Additional relevant MeSH terms: Systolic Murmurs

Study Results

Participant Flow

Arm/Group Title	Intensive Control of SBP	Standard Control of SBP
Arm/Group Description	Participants randomized into the Intensive BP arm had a goal of SBP <120 mm Hg. 2-drug therapy initiated in most 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 visits: addition of another drug "required" if not at goal. Intensive control of SBP: Use of once-daily antihypertensive agents was encouraged unless alternative frequency was necessary. One or more medications from the following classes of agents were provided by the study for use in managing participants in both 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	Participants randomized into the Standard arm had 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 Standard control of SBP: The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Period Title: Overall Study
STARTED	4678	4683
COMPLETED	4678	4683
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intensive Control of SBP	Standard Control of SBP	Total
Arm/Group Description	Participants randomized into the Intensive BP arm had a goal of SBP <120 mm Hg. 2-drug therapy initiated in most 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 visits: addition of another drug "required" if not at goal. Intensive control of SBP: Use of once-daily antihypertensive agents was encouraged unless alternative frequency was necessary. One or more medications from the following classes of agents were provided by the study for use in managing participants in both 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	Participants randomized into the Standard arm had 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 Standard control of SBP: The same medications used in the Intensive BP arm will be used for the Standard BP arm.	Total of all reporting groups
Overall Participants	4678	4683	9361
Age (year) [Mean (Standard Deviation) ]
Age overall	67.9 (9.4)	67.9 (9.5)	67.9 (9.4)
Sex: Female, Male (Count of Participants)
Female	1684 36%	1648 35.2%	3332 35.6%
Male	2994 64%	3035 64.8%	6029 64.4%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic black	1379 29.5%	1423 30.4%	2802 29.9%
Hispanic	503 10.8%	481 10.3%	984 10.5%
Non-Hispanic white	2698 57.7%	2701 57.7%	5399 57.7%
Other	98 2.1%	78 1.7%	176 1.9%
Estimated GFR (ml/min/1.73 m2) [Mean (Standard Deviation) ]
Among all participants	71.8 (20.7)	71.7 (20.5)	71.7 (20.6)
Among those with estimated GFR >= 60 ml/min/1.73 m	81.3 (15.5)	81.1 (15.5)	81.2 (15.5)
Among those with estimated GFR < 60 ml/min/1.73 m	47.8 (9.5)	47.9 (9.5)	47.8 (9.5)
Criterion for increased cardiovascular risk (Count of Participants)
Age > 75 years	1317 28.2%	1319 28.2%	2636 28.2%
Chronic kidney disease	1330 28.4%	1316 28.1%	2646 28.3%
Cardiovascular disease	940 20.1%	937 20%	1877 20.1%
Cardiovascular disease clinical	779 16.7%	783 16.7%	1562 16.7%
Cardiovascular disease subclinical	247 5.3%	246 5.3%	493 5.3%
Framingham CVD risk score >= 15%	2870 61.4%	2867 61.2%	5737 61.3%
Black race (Count of Participants)
Count of Participants [Participants]	1454 31.1%	1493 31.9%	2947 31.5%
Baseline BP mm Hg (mm Hg) [Mean (Standard Deviation) ]
Systolic	139.7 (15.8)	139.7 (15.4)	139.7 (15.6)
Diastolic	78.2 (11.9)	78.0 (12.0)	78.1 (11.9)
Distribution of systolic blood pressure (Count of Participants)
< 132 mm Hg	1583 33.8%	1553 33.2%	3136 33.5%
> 132 mm Hg to < 145 mm Hg	1489 31.8%	1549 33.1%	3038 32.5%
> 145 mm Hg	1606 34.3%	1581 33.8%	3187 34%
Serum creatinine (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	1.07 (0.34)	1.08 (0.34)	1.07 (0.34)
Ratio of urinary albumin (mg) to creatinine (g) (ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio]	44.1 (178.7)	41.1 (152.9)	42.6 (166.3)
Fasting total cholesterol - mg/dl (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	190.2 (41.4)	190.0 (40.9)	190.1 (41.2)
Fasting HDL cholesterol - mg/dl (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	52.9 (14.3)	52.8 (14.6)	52.9 (14.5)
Fasting total triglycerides - mg/dl (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	124.8 (85.8)	127.1 (95.0)	125.9 (90.5)
Fasting plasma glucose - mg/dl (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	98.8 (13.7)	98.8 (13.4)	98.8 (13.5)
Statin use (Count of Participants)
Statin Use	1978 42.3%	2076 44.3%	4054 43.3%
No Statin Use	2667 57%	2564 54.8%	5231 55.9%
Unknown Statin Use	33 0.7%	43 0.9%	76 0.8%
Aspirin use (Count of Participants)
Aspirin Use	2406 51.4%	2350 50.2%	4756 50.8%
No Aspirin Use	2255 48.2%	2316 49.5%	4571 48.8%
Unknown Aspirin Use	17 0.4%	17 0.4%	34 0.4%
Smoking status - no. (%) (Count of Participants)
Never smoked	2050 43.8%	2072 44.2%	4122 44%
Former smoker	1977 42.3%	1996 42.6%	3973 42.4%
Current smoker	639 13.7%	601 12.8%	1240 13.2%
Missing data	12 0.3%	14 0.3%	26 0.3%
Framingham 10-yr cardiovascular disease risk score (probability) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [probability]	24.8 (12.6)	24.8 (12.5)	24.8 (12.5)
Body-mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.9 (5.8)	29.8 (5.7)	29.9 (5.8)
Antihypertensive agents - no./patient (agents per patient) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [agents per patient]	1.8 (1.0)	1.8 (1.0)	1.8 (1.0)
Not using antihypertensive agents - no. (%) (Count of Participants)
Count of Participants [Participants]	432 9.2%	450 9.6%	882 9.4%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Control of SBP	Standard Control of SBP
Arm/Group Description	Participants randomized into the Intensive BP arm had a goal of SBP <120 mm Hg. 2-drug therapy initiated in most 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 visits: addition of another drug "required" if not at goal. Intensive control of SBP: Use of once-daily antihypertensive agents was encouraged unless alternative frequency was necessary. One or more medications from the following classes of agents were provided by the study for use in managing participants in both 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	Participants randomized into the Standard arm had 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 Standard control of SBP: The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Measure Participants	4678	4683
Count of Participants [Participants]	243 5.2%	319 6.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Control of SBP, Standard Control of SBP
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.64 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With All-cause Mortality
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Control of SBP	Standard Control of SBP
Arm/Group Description	Participants randomized into the Intensive BP arm had a goal of SBP <120 mm Hg. 2-drug therapy initiated in most 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 visits: addition of another drug "required" if not at goal. Intensive control of SBP: Use of once-daily antihypertensive agents was encouraged unless alternative frequency was necessary. One or more medications from the following classes of agents were provided by the study for use in managing participants in both 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	Participants randomized into the Standard arm had 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 Standard control of SBP: The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Measure Participants	4678	4683
Count of Participants [Participants]	155 3.3%	210 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Control of SBP, Standard Control of SBP
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.60 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of CKD Participants Who Experienced a 50% Decline From Baseline eGFR
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

Participants with CKD at baseline

Arm/Group Title	Intensive Control of SBP	Standard Control of SBP
Arm/Group Description	Participants randomized into the Intensive BP arm had a goal of SBP <120 mm Hg. 2-drug therapy initiated in most 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 visits: addition of another drug "required" if not at goal. Intensive control of SBP: Use of once-daily antihypertensive agents was encouraged unless alternative frequency was necessary. One or more medications from the following classes of agents were provided by the study for use in managing participants in both 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	Participants randomized into the Standard arm had 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 Standard control of SBP: The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Measure Participants	1330	1316
Count of Participants [Participants]	10 0.2%	12 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Control of SBP, Standard Control of SBP
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.34 to 1.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Participants Who Developed End Stage Renal Disease
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Control of SBP	Standard Control of SBP
Arm/Group Description	Participants randomized into the Intensive BP arm had a goal of SBP <120 mm Hg. 2-drug therapy initiated in most 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 visits: addition of another drug "required" if not at goal. Intensive control of SBP: Use of once-daily antihypertensive agents was encouraged unless alternative frequency was necessary. One or more medications from the following classes of agents were provided by the study for use in managing participants in both 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	Participants randomized into the Standard arm had 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 Standard control of SBP: The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Measure Participants	4678	4683
Count of Participants [Participants]	12 0.3%	8 0.2%

5. Secondary Outcome

Title	Number of Patients With All-cause Dementia
Description	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).
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

Participants who completed at least 1 cognitive assessment during follow-up

Arm/Group Title	Intensive Control of SBP	Standard Control of SBP
Arm/Group Description	Participants randomized into the Intensive BP arm had a goal of SBP <120 mm Hg. 2-drug therapy initiated in most 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 visits: addition of another drug "required" if not at goal. Intensive control of SBP: Use of once-daily antihypertensive agents was encouraged unless alternative frequency was necessary. One or more medications from the following classes of agents were provided by the study for use in managing participants in both 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	Participants randomized into the Standard arm had 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 Standard control of SBP: The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Measure Participants	4278	4285
Count of Participants [Participants]	149 3.2%	176 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Control of SBP, Standard Control of SBP
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.10
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Small Vessel Cerebral Ischemic Disease
Description	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
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Of the 670 participants with WML volume measurement at baseline, 462 completed the follow-up MRI. Image quality control requirements were not met for 13 participants with a follow-up MRI scan, resulting in a sample of 449 adults.

Arm/Group Title	Intensive Control of SBP	Standard Control of SBP
Arm/Group Description	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. Intensive control of SBP: 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.	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 Standard control of SBP: 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.
Measure Participants	200	249
Change in total white matter lesion volume from ba	0.23	0.37
Change in total brain volume from baseline	-7.7	-6.8

Adverse Events

Time Frame	Includes Serious Adverse Events (SAEs) reported after randomization and throughout the duration of the trial, mean follow-up was 3.26 years.
Adverse Event Reporting Description	Adverse event reporting included occurrence of acute kidney injury or acute renal failure and specific monitored conditions if they were evaluated in emergency departments (hypotension, syncope, injurious falls, electrolyte abnormalities, bradycardia).
Arm/Group Title	Intensive Control of SBP		Standard Control of SBP
Arm/Group Description	Participants randomized into the Intensive BP arm had a goal of SBP <120 mm Hg. 2-drug therapy initiated in most 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 visits: addition of another drug "required" if not at goal. Intensive control of SBP: Use of once-daily antihypertensive agents was encouraged unless alternative frequency was necessary. One or more medications from the following classes of agents were provided by the study for use in managing participants in both 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		Participants randomized into the Standard arm had 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 Standard control of SBP: The same medications used in the Intensive BP arm will be used for the Standard BP arm.
All Cause Mortality
	Intensive Control of SBP		Standard Control of SBP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	155/4678 (3.3%)		210/4683 (4.5%)
Serious Adverse Events
	Intensive Control of SBP		Standard Control of SBP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1793/4678 (38.3%)		1736/4683 (37.1%)
Cardiac disorders
Chest Pain	198/4678 (4.2%)		191/4683 (4.1%)
Tachyarrhythmia	141/4678 (3%)		176/4683 (3.8%)
Other ischaemic heart disease	170/4678 (3.6%)		182/4683 (3.9%)
Cardiac failure	58/4678 (1.2%)		98/4683 (2.1%)
Myocardial infarcation	70/4678 (1.5%)		106/4683 (2.3%)
Hypertension	58/4678 (1.2%)		69/4683 (1.5%)
Cardiac pacemaker insertion	33/4678 (0.7%)		39/4683 (0.8%)
General disorders
Death	155/4678 (3.3%)		210/4683 (4.5%)
Dehydration	51/4678 (1.1%)		41/4683 (0.9%)
Other	952/4678 (20.4%)		951/4683 (20.3%)
Infections and infestations
Cellulitis	40/4678 (0.9%)		30/4683 (0.6%)
Sepsis	36/4678 (0.8%)		40/4683 (0.9%)
Musculoskeletal and connective tissue disorders
Knee arthroplasty	138/4678 (2.9%)		119/4683 (2.5%)
Hip arthroplasty	67/4678 (1.4%)		81/4683 (1.7%)
Spinal fusion surgery	46/4678 (1%)		30/4683 (0.6%)
Spinal laminectomy	36/4678 (0.8%)		32/4683 (0.7%)
Nervous system disorders
Dizziness	34/4678 (0.7%)		25/4683 (0.5%)
Renal and urinary disorders
Urinary tract infection	48/4678 (1%)		47/4683 (1%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	100/4678 (2.1%)		114/4683 (2.4%)
Chronic obstructive pulmonary disease	42/4678 (0.9%)		64/4683 (1.4%)
Dyspnoea	48/4678 (1%)		45/4683 (1%)
Vascular disorders
Ischaemic cerebrovascular conditions	109/4678 (2.3%)		121/4683 (2.6%)
Pulmonary embolism	34/4678 (0.7%)		32/4683 (0.7%)
Pulmonary embolism	32/4678 (0.7%)		31/4683 (0.7%)
Other (Not Including Serious) Adverse Events
	Intensive Control of SBP		Standard Control of SBP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1399/4678 (29.9%)		1342/4683 (28.7%)
Cardiac disorders
Hypotension	48/4678 (1%)		27/4683 (0.6%)
General disorders
Electrolyte Abnormality	33/4678 (0.7%)		22/4683 (0.5%)
Injurious fall	229/4678 (4.9%)		222/4683 (4.7%)
Serum sodium < 130 mmol/liter	180/4678 (3.8%)		100/4683 (2.1%)
Serum sodium > 150 mmol/liter	6/4678 (0.1%)		0/4683 (0%)
Serum potassium <3.0 mmol/liter	114/4678 (2.4%)		74/4683 (1.6%)
Serum potassium >5.5 mmol/liter	176/4678 (3.8%)		171/4683 (3.7%)
Nervous system disorders
Syncope	56/4678 (1.2%)		33/4683 (0.7%)
Orthostatic hypotension alone	777/4678 (16.6%)		857/4683 (18.3%)
Orthostatic hypotension with dizziness	62/4678 (1.3%)		71/4683 (1.5%)
Renal and urinary disorders
Acute kidney injury or acute renal failure	11/4678 (0.2%)		3/4683 (0.1%)
Vascular disorders
Bradycardia	17/4678 (0.4%)		10/4683 (0.2%)

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.