Effect of Intense vs. Standard Hypertension Management on Nighttime Blood Pressure - an Ancillary Study to SPRINT

Study Overview
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Brief Summary
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Hypertension is a major risk factor for cardiovascular and renal disease, and a leading cause of premature mortality worldwide. Early hypertension studies showed that treating elevated blood pressure (BP) reduces patients' risk of cardiovascular disease and all-cause mortality. In subsequent research, patients achieved greater improvement in cardiovascular outcomes when their treatment was aimed at a moderate systolic BP target (<150mmHg) than at higher targets. Although observational data suggest that even lower BP targets may be beneficial, this has not been seen in randomized trials; instead, intense treatment of hypertension (i.e., to a target systolic BP <120mmHg) was found to have no effect on participants' risk for renal disease, cardiovascular disease, or all-cause mortality. One potential explanation for this apparent lack of benefit of intense BP targets is that the study protocols targeted reductions in clinic BP rather than ambulatory BP. Ambulatory BP monitoring (ABPM) allows for assessment of BP throughout the day and night. Of all the BP measurements, nighttime systolic BP appears to be the best predictor of cardiovascular disease and all-cause mortality. Because recent trials assessing intense BP targets did not include ambulatory BP measurements, the effect of intensive treatment on nighttime BP is largely unknown. To address this important gap in knowledge, we will conduct ABPM in 600 participants as part of an ancillary study to the ongoing Systolic Blood Pressure Intervention Trial (SPRINT). The goal of the ancillary study is to evaluate the effect of intensive vs. standard clinic based BP targets on nighttime BP (primary outcome), as well as night/day BP ratio, timing of peak BP, 24hr BP, and BP variability (secondary outcomes). The SPRINT trial includes approximately 9250 participants at high risk for cardiovascular disease. The investigators hypothesize that intense targeting of clinic systolic BP does not lower nighttime systolic BP compared to a standard target.

Official Title
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Effect of Intense vs. Standard Hypertension Management on Nighttime Blood Pressure

Conditions
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Hypertension

Intervention / Treatment
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* Other: Intensive BP Arm
* Other: Standard BP arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: eligible and enrolled in SPRINT at the 27 month follow up visit able and willing to provide informed consent Exclusion Criteria: arm circumference >50cm shift worker or work regularly at night history of breast cancer requiring mastectomy end-stage renal disease

Ages Eligible for Study
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Minimum Age: 55 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive BP Arm<br>Participants randomized into the Intensive BP arm will have a goal of SBP <120mmHg. Drugs will be added and/or titrated at each visit (monthly) to achieve SBP <120 mmHg. At periodic milepost visits, addition of another drug will be required if not at goal. | Other: Intensive BP Arm<br>* Participants in the Intensive arm have a goal of SBP <120 mmHg.<br>|
| Active Comparator: Standard BP Arm<br>Participants randomized into the Standard arm will have a goal of SBP <140 mm Hg. Intensify therapy if SBP ≥160 mmHg @ 1 visit; ≥140 mmHg @ 2 consecutive visits; Down-titration if SBP <130 mmHg @ 1 visit; <135 mmHg @ 2 consecutive visits. | Other: Standard BP arm<br>* Participants in the Standard BP arm have a goal of SBP <140 mmHg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nighttime systolic blood pressure | Ambulatory blood pressure monitoring will be performed within 3 weeks of the 27 month follow up visit. For the primary analysis, nighttime BP will be defined by narrow clock time (01:00 AM to 6:00 AM). | 27 month follow up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Night to day systolic BP ratio | Ambulatory blood pressure monitoring will be performed within 3 weeks of the 27 month follow up visit. The night to day systolic BP ratio will be calculated using narrow clock times. | 27 month follow up visit | 
| Timing of peak BP | Ambulatory blood pressure monitoring will be performed within 3 weeks of the 27 month follow up visit. The timing of the peak BP will be calculated for each subject using cosinor rhythmometry analysis. | 27 month follow up visit | 
| 24hr average systolic BP | Ambulatory blood pressure monitoring will be performed within 3 weeks of the 27 month follow up visit. The average systolic BP will be calculated for each subject. | 27 month follow up visit | 
| Blood pressure variability | Ambulatory blood pressure monitoring will be performed within 3 weeks of the 27 month follow up visit. Blood pressure variability will be defined by the standard deviation of the systolic blood pressure and by calculating the average real variability (ARV). | 27 month follow up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Nighttime blood pressure