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

NCT02232880 | Terminated Phase 2 Results DMC

• 1 other identifier: 121740
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

hypertension; inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in Blood Pressure

  6 months

• Change in Brachial Artery Reactivity

  6 months

• Change in Inflammatory Markers

  6 months

Study Arms (2)

abatacept

ACTIVE COMPARATOR

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

placebo

PLACEBO COMPARATOR

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

Interventions

Abatacept DRUG

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.

Also known as: Orencia

abatacept

Placebo DRUG

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.

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6602, United States

Location

MeSH Terms

Conditions

Hypertension; Inflammation

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Limitations and Caveats

No patients received treatment prior to study termination.

Results Point of Contact

• Title: David Harrison
• Organization: Vanderbilt University

david.g.harrison@Vanderbilt.Edu

Study Officials

• David G Harrison, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2014
• First Posted: September 5, 2014
• Study Start: August 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 7, 2017
• Results First Posted: August 29, 2016

Record last verified: 2016-12

Locations

US (1)