Hypertension
Conditions
Keywords
hypertension, inflammation
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.
Interventions
DRUGAbatacept
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.
DRUGPlacebo
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.
Sponsors
Bristol-Myers Squibb
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure From Randomization to End of Treatment | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Pressure | 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 |
| Change in Brachial Artery Reactivity | 6 months | change in brachial artery reactivity measured at randomization and after 24 weeks of treatment |
| Change in Inflammatory Markers | 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 |
Countries
United States
Participant flow
Pre-assignment details
One participant was consented. The study terminated before the participant was randomized. No participants received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Consented Patients No patients received treatment prior to study termination | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | study stopped prior to randomization | 1 |
Baseline characteristics
| Characteristic | Consented Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Gender Female | 1 Participants |
| Gender Male | 0 Participants |
| Region of Enrollment United States | 1 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
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.
Time frame: 6 months
Population: No patients received treatment prior to study termination
Secondary
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
Time frame: 6 months
Population: No patients received treatment prior to study termination.
Secondary
Change in Brachial Artery Reactivity
change in brachial artery reactivity measured at randomization and after 24 weeks of treatment
Time frame: 6 months
Population: No patients received treatment prior to study termination
Secondary
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
Time frame: 6 months
Population: No patients received treatment prior to study termination