Treatment of Resistant Hypertension by Prevention of T-Cell Co-Stimulation

The purpose of this study is to test whether abatacept, a drug approved by the Food and Drug Administration to treat rheumatoid arthritis, may help blood pressure medications to work better. This will be studied in people with high blood pressure that is not well controlled on three or more blood pressure medications, the condition also known as resistant hypertension. We expect to show that adding abatacept therapy to standardized treatment of resistant hypertension will result in a greater decrease in blood pressure at 24 weeks compared to treatment with placebo and conventional blood pressure treatment.

Study Overview

• Status: Terminated
• Conditions: Hypertension
• Intervention / Treatment: Drug: Abatacept; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6602
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women 18 to 65 years of age with hypertension, treated with three or more anti-hypertensive drugs, one being a diuretic, and
• having a systolic blood pressure >150 mmHg in the clinic and daytime average >150 mmHg on ambulatory blood pressure monitoring

Exclusion Criteria:

• Medical history of secondary cause of hypertension, severe obesity (BMI >35), severe psychiatric disorders, cancer in the last 5 years other than nonmelanoma skin cell cancers, herpes zoster or cytomegalovirus that resolved less than 2 months before
• Inability to return for abatacept treatment and follow-up for 24 weeks.
• Inability to understand or complete study-related assessments.
• Current abuse of drugs or alcohol.
• Receipt of any live vaccines within 3 months of the anticipated first dose of study medication.
• Evidence of active or latent bacterial or viral infections at the time of potential enrollment, including human immunodeficiency virus (HIV)
• Risk for tuberculosis
• Abnormal laboratory values including positive hepatitis B surface antigen, hemoglobin < 8.5 g/dL, white blood cell count < 3000/mm3, platelets < 100,000/mm3, creatinine > 2.5 times the upper limit of normal (ULN), alanine aminotransferase or aspartate aminotransferase > 2 times the ULN.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: abatacept; Subjects randomized to abatacept weighing 60 to 100 kg will receive 750 mg, and those >100 kg will receive 1000 mg abatacept by intravenous infusion at 0 [randomization], 2, and 4 weeks and then every 4 weeks thereafter for a total of 24 weeks. All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.	Drug: Abatacept; All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.; Other Names: Orencia
Placebo Comparator: placebo; Subjects randomized to placebo will receive 100 ml normal saline by intravenous infusion at 0 [randomization], 2, and 4 weeks and then every 4 weeks thereafter for a total of 24 weeks. All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.	Drug: Placebo; All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Systolic Blood Pressure From Randomization to End of Treatment	Ambulatory blood pressure monitoring will be used at the end of the 4 weeks standardized treatment and at the end of 6 months randomized treatment with abatacept or placebo. The change in systolic blood pressure from these 2 recordings will be the primary endpoint.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood Pressure	Changes in the rate of change of blood pressure estimated by automated in office cuff measurements and ambulatory blood pressure at 12 weeks after randomization	6 months
Change in Brachial Artery Reactivity	change in brachial artery reactivity measured at randomization and after 24 weeks of treatment	6 months
Change in Inflammatory Markers	changes in plasma and T cell markers of activation and T cell cytokine production from randomization to end of 24 weeks of treatment	6 months

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: David G Harrison, MD, Vanderbilt University

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: August 12, 2014
• First Submitted That Met QC Criteria: September 2, 2014
• First Posted (Estimate): September 5, 2014

Study Record Updates

• Last Update Posted (Estimate): February 7, 2017
• Last Update Submitted That Met QC Criteria: December 14, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: hypertension; inflammation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: 121740

Plan for Individual participant data (IPD)

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