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Resistant hypertension (RH) is characterized by high blood pressure (BP) in spite of concurrent use of three or more antihypertensive agents of different classes, combined at optimal doses. Currently it has been largely discussed the influence of inflammation in RH. The BP variation promotes increased expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukins 1 and 6. It was showed that treatment with TNF-α inhibitor improves BP and endothelial function, and reduces arterial stiffness in patients with rheumatoid arthritis. Recently, it was demonstrated that TNF-α levels are increased in RH subjects compared to normotensives. This study aims to assess whether the acute inhibition of TNF-α changes hemodynamic parameters, such as mean BP levels in RH.
This crossover, double-blind study will include 12 resistant hypertensive subjects - regularly followed at the Outpatient Resistant Hypertension Clinic/UNICAMP - which will randomized assigned to (1) saline infusion followed by infliximab infusion (TNF-α inhibitor, 3 mg/kg) and (2) infliximab followed by saline, for two hours and washout of the 40-day period between both infusions. It is expected that the TNF-α inhibition regulates hemodynamic parameters, such as mean BP, cardiac Output, total peripheral resistance, which may allow a better rational approach for the RH treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TNF-alpha inhibitor drug | Active Comparator | Infliximab infusion (TNF-α inhibitor, 3 mg/kg, 250mL) |
|
| Placebo drug | Placebo Comparator | Saline infusion (250mL) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Infliximab | Biological | Monoclonal antibody biologic drug that inhibits tumour necrosis factor alpha (TNF-α), 3 mg/kg for 2 hours (250mL) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean blood pressure in mmHg | Mean blood pressure will be simultaneously assessed for 15 minutes in baseline, during and post the infusions | 15 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Cardiac hypertrophy in g/m² | Left ventricular mass index will be determined by echocardiography in baseline and post-1 week of the infusions | Baseline and post-1 week of the infusions |
| Endothelial function in percentage |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ana Paula Faria, PhD | University of Campinas | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Campinas (UNICAMP) | Campinas | São Paulo | 13083970 | Brazil |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069285 | Infliximab |
| D048069 | Tumor Necrosis Factors |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
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|
| Saline | Other | Saline for 2 hours (250mL) |
|
Endothelial function will be assessed by flow-mediated dilation in baseline and post-1 week of the infusions
| Baseline and post-1 week of the infusions |
| Arterial stiffness in m/s | Arterial stiffness will be determined by pulse wave velocity in baseline and post-1 week of the infusions | Baseline and post-1 week of the infusions |
| Tumor necrosis factor-alpha in pg/mL | Plasma concentration of tumor necrosis factor-alpha will be determined by ELISA | Baseline and post-1 week of the infusions |
| Interleukin-6 | Plasma concentration of Interleukin-6 will be determined by ELISA | Baseline and post-1 week of the infusions |
| Interleukin-10 | Plasma concentration of Interleukin-10 will be determined by ELISA | Baseline and post-1 week of the infusions |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |