Mechanisms of Increased Ambulatory Blood Pressure in Patients With Intradialytic Hypertension

Study Overview
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Brief Summary
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The purpose of this study is 1) to determine what physiologic factors (extracellular fluid overload or vasoconstriction) contribute more to increased blood pressure levels between dialysis treatments in hemodialysis patients whose blood pressure increases and decreases during hemodialysis and 2) to determine whether carvedilol provides better control of blood pressure between dialysis treatments than prazosin in patients whose blood pressure increases during dialysis.

Official Title
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Mechanism of Increased Ambulatory Blood Pressure in Patients With Intradialytic Hypertension and Hemodialysis Controls: A Case Control Study and Crossover Trial Comparing Carvedilol and Prazosin Hydrochloride

Conditions
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Intradialytic Hypertension

Intervention / Treatment
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* Drug: Carvedilol vs. Prazosin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (for Aims 1 and 2): age more than 18 years Hypertension defined as systolic blood pressure more than 140 mmHg before dialysis or more than 130 mmHg after dialysis For case subjects with intradialytic hypertension: systolic blood pressure increase more than 10 mmHg from pre to post dialysis in at least 4 out of 6 screening treatments For control subjects: systolic blood pressure decrease more than 10 mmHg from pre to post dialysis in at least 4 out of 6 screening treatments Inclusion criteria for Aim 3 includes the case subjects described above. Exclusion Criteria: For Aims 1 and 2: Hemodialysis vintage less than 1 month Amputated arm or leg Presence of cardiac defibrillator or pacemaker Presence of large metal prosthesis Failure to achieve dry weight For Case subjects participating in Aim 3: Patients with a specific indication for beta blocker therapy including systolic heart failure, history of myocardial infarction, history of tachyarrhythmia or angina being managed with beta blocker therapy. Patients with contraindications to beta blockade including bradycardia (heart rate less than 60 beats per minute) while not on a pulse lowering drug, severe reactive airway disease, prior intolerance to beta blocker therapy Prior intolerance to alpha blocker therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Carvedilol (for Aim 3 only)<br>Eligible case subjects from aims 1-2 will participate in a randomized crossover study where each subject will receive carvedilol and prazosin for 8 weeks each(under randomized treatment sequence) with a 1 week washout period included in between treatments. The first arm will include subjects that are assigned to the randomization sequence: Carvedilol x 8 weeks (titrated up to 50 mg po bid), washout x 1 week, Prazosin x 8 weeks (titrated up to 16 mg daily) | Drug: Carvedilol vs. Prazosin<br> <br> |
| Prazosin (for Aim 3 only)<br>Eligible case subjects from aims 1-2 will participate in a randomized crossover study where each subject will receive carvedilol and prazosin for 8 weeks each(under randomized treatment sequence) with a 1 week washout period included in between treatments. The first arm will include subjects that are assigned to the randomization sequence: Prazosin x 8 weeks, washout x 1 week, Carvedilol x 8 weeks | Drug: Carvedilol vs. Prazosin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of Extracellular Body Water to Total Body Water |  | Expected recruitment is 4-5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endothelin-1 from pre to post dialysis |  | Expected recruitment is 4-5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intradialytic Hypertension, Hemodialysis, Hypertension, Extracellular Volume, Endothelial Cell Dysfunction, Endothelin 1, Carvedilol