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

• ClinicalTrials.gov Identifier: NCT02232880
• Recruitment Status: Terminated
• First Posted: September 5, 2014
• Results First Posted: August 29, 2016
• Last Update Posted: February 7, 2017
• Sponsor: Vanderbilt University Medical Center
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Vanderbilt University Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: Abatacept; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Treatment of Resistant Hypertension by Prevention of T-Cell Co-Stimulation
• Study Start Date: August 2014
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: June 2015

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in Systolic Blood Pressure From Randomization to End of Treatment [ Time Frame: 6 months ]
   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.

Secondary Outcome Measures :

1. Change in Blood Pressure [ Time Frame: 6 months ]
   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
2. Change in Brachial Artery Reactivity [ Time Frame: 6 months ]
   change in brachial artery reactivity measured at randomization and after 24 weeks of treatment
3. Change in Inflammatory Markers [ Time Frame: 6 months ]
   changes in plasma and T cell markers of activation and T cell cytokine production from randomization to end of 24 weeks of treatment

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232-6602

Sponsors and Collaborators

Vanderbilt University Medical Center

Bristol-Myers Squibb

Investigators

• Principal Investigator: David G Harrison, MD; Vanderbilt University

More Information

• Responsible Party: Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT02232880
• Other Study ID Numbers: 121740
• First Posted: September 5, 2014
• Results First Posted: August 29, 2016
• Last Update Posted: February 7, 2017
• Last Verified: December 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Vanderbilt University Medical Center:

hypertension; inflammation

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Abatacept; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents