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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Other: Intensive BP Arm; Other: Standard BP arm

• Study Type: Interventional
• Enrollment (Actual): 897
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Washington DC VA medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44129
      • Louis Stokes Cleveland VA Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Memphis VA
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77030
      • Houston VA
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive BP Arm; 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; Participants in the Intensive arm have a goal of SBP <120 mmHg.
Active Comparator: Standard BP Arm; 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; Participants in the Standard BP arm have a goal of SBP <140 mmHg.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Mayo Clinic; University of Pennsylvania; University of Alabama at Birmingham; Vanderbilt University; University of Utah; Louis Stokes VA Medical Center; Michael E. DeBakey VA Medical Center; Carolinas Medical Center; Washington D.C. Veterans Affairs Medical Center; Wake Forest University; Memphis VA Medical Center
• Investigators: Principal Investigator: Paul E Drawz, MD, MHS, MS, University of Minnesota

Publications and helpful links

General Publications

• Drawz PE, Pajewski NM, Bates JT, Bello NA, Cushman WC, Dwyer JP, Fine LJ, Goff DC Jr, Haley WE, Krousel-Wood M, McWilliams A, Rifkin DE, Slinin Y, Taylor A, Townsend R, Wall B, Wright JT, Rahman M. Effect of Intensive Versus Standard Clinic-Based Hypertension Management on Ambulatory Blood Pressure: Results From the SPRINT (Systolic Blood Pressure Intervention Trial) Ambulatory Blood Pressure Study. Hypertension. 2017 Jan;69(1):42-50. doi: 10.1161/HYPERTENSIONAHA.116.08076. Epub 2016 Nov 14.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: April 16, 2013
• First Submitted That Met QC Criteria: April 16, 2013
• First Posted (Estimate): April 18, 2013

Study Record Updates

• Last Update Posted (Actual): January 25, 2019
• Last Update Submitted That Met QC Criteria: January 23, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Hypertension; Nighttime blood pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 1303M30341 (Other Identifier: University of Minnesota IRB)