Back to resultsTreatment of Resistant Hypertension by Prevention of T-Cell Co-Stimulation
Primary Purpose
Hypertension
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Abatacept
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension focused on measuring hypertension, inflammation
Eligibility 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.
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
abatacept
placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
Change in Brachial Artery Reactivity
change in brachial artery reactivity measured at randomization and after 24 weeks of treatment
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
Full Information
NCT ID
NCT02232880
First Posted
August 12, 2014
Last Updated
December 14, 2016
Sponsor
Vanderbilt University Medical Center
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT02232880
Brief Title
Treatment of Resistant Hypertension by Prevention of T-Cell Co-Stimulation
Official Title
Treatment of Resistant Hypertension by Prevention of T-Cell Co-Stimulation
Study Type
Interventional
2. Study Status
Record Verification Date
December 2016
Overall Recruitment Status
Terminated
Why Stopped
failure to recruit
Study Start Date
August 2014 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
hypertension, inflammation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
abatacept
Arm Type
Active Comparator
Arm Description
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.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Abatacept
Other Intervention Name(s)
Orencia
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Systolic Blood Pressure From Randomization to End of Treatment
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change in Blood Pressure
Description
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
Time Frame
6 months
Title
Change in Brachial Artery Reactivity
Description
change in brachial artery reactivity measured at randomization and after 24 weeks of treatment
Time Frame
6 months
Title
Change in Inflammatory Markers
Description
changes in plasma and T cell markers of activation and T cell cytokine production from randomization to end of 24 weeks of treatment
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David G Harrison, MD
Organizational Affiliation
Vanderbilt University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6602
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Treatment of Resistant Hypertension by Prevention of T-Cell Co-Stimulation
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