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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Abatacept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: abatacept<br>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<br>* 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.<br>* Other names: Orencia;|
| Placebo Comparator: placebo<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension, inflammation