Regulating Blood Pressure During Recovery From Intracerebral Hemorrhage and Ischemic Stroke (REDUCE)

The purpose of this research study is to determine whether blood pressure treatment regimens with spironolactone are better than blood pressure treatment regimens without spironolactone at lowering blood pressure in stroke survivors.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Intracerebral Hemorrhage; Spironolactone
• Intervention / Treatment: Drug: Spironolactone Pill

Detailed Description

This is a pragmatic, randomized, open-label, blinded-endpoint trial comparing spironolactone-containing antihypertensive regimens versus standard antihypertensive regimens based on the 2017 AHA/ACC guidelines in stroke survivors.

This study will randomize a total of 200 patients, 100 white and 100 non-white patients, at least three weeks after last known normal or symptom discovery/onset of their stroke to an antihypertensive regimen with spironolactone once daily or standard BP control based on the 2017 AHA/ACC guidelines for 1 year.

Participants will undergo baseline testing for neurohormonal levels and will be followed for 12 months with regular assessment of home BP readings. The primary outcome of home systolic BP will be measured at 3 months.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06512
      • Recruiting
      • Yale New Haven Hospital
      • Contact: Kevin Sheth, MD; Phone Number: 203-737-8051; Email: kevin.sheth@yale.edu
      • Principal Investigator: Kevin Sheth, MD
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Health
      • Contact: Cheryl D Bushnell, MD, MHS; Phone Number: 336-716-2357; Email: cbushnel@wakehealth.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Recruiting
      • Temple University Hospital
      • Contact: Michael Mullen, MD; Phone Number: 215-707-3040; Email: michael.mullen@tuhs.temple.edu
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Hospital of the University of Pennsylvania
      • Contact: Debbie Cohen; Phone Number: 215-662-7544; Email: Debbie.Cohen@pennmedicine.upenn.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas Health Science Center at Houston
      • Contact: Munachi N. Okpala, DNP; Phone Number: 713-417-9366; Email: munachi.n.okpala@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Symptomatic ICH confirmed by head CT or brain MRI during hospitalization OR ischemic stroke patients. Ischemic stroke will be defined by focal signs/symptoms of any duration associated with evidence of acute arterial infarction on neuroimaging or clinical evidence of cerebral focal arterial ischemic injury with symptoms persisting ≥ 24 hours.
3. Written, informed consent by patient or surrogate
4. Ability to comply with all study procedures and available for the duration of the study

Exclusion Criteria:

1. Secondary ICH due to trauma, vascular malformation, or tumor
2. Life expectancy < 1 year
3. eGFR <45
4. Serum potassium greater than or equal to the upper limit of normal of the lab on the two most recent consecutive potassium levels prior to enrollment
5. Known hypersensitivity to spironolactone
6. Upper arm greater than 17 inches in circumference
7. Pregnancy, planned pregnancy, or breastfeeding
8. Contraindication to discontinuing mineralocorticoid antagonist therapy for 3-12 months per the investigator's discretion (e.g., refractory proteinuria)
9. Systolic BP >200 mmHg or diastolic BP >110 mmHg at the time of randomization
10. Systolic BP <120 mmHg at the time of randomization
11. Any condition which, in the judgement of the investigator, increases the risk to the patient
12. History of Addison's disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Spironolactone; Participants randomized to the Spironolactone arm will be receiving Spironolactone in addition to their normal routine blood pressure treatment.	Drug: Spironolactone Pill; Participants randomized to the Spironolactone arm will be receiving Spironolactone in addition to their normal routine blood pressure treatment.
No Intervention: Standard Care; Participants randomized to the Standard care arm will be receiving their normal routine blood pressure treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average change in home systolic blood pressure at 3 months	The average home systolic blood pressure will be measured using a home blood pressure cuff	Baseline, 3 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving BP < 130/80 mm Hg	The proportion of patients achieving BP < 130/80 mm Hg at 3 months will be measured	3 months
Number of antihypertensive medications at 3 months	The number of antihypertensive medications at 3 months will be collected	3 months
Number of antihypertensive medications at 1 year	The number of antihypertensive medications at 1 year will be collected	1 year
Stroke, myocardial infarction, or death	Incidence of stroke of any type (ischemic or hemorrhagic), myocardial infarction, or death from any cause	1 year
Change in modified Rankin Scale score	Measure of neurologic disability (0=no disability to 6=dead)	Baseline, 1 year

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: American Heart Association

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Intracranial Hemorrhages; Stroke; Ischemic Stroke; Ischemia; Hemorrhage; Cerebral Infarction; Cerebral Hemorrhage; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: 2000029811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No