Mechanisms of Increased Ambulatory Blood Pressure in Patients With Intradialytic Hypertension

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT01862497

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

62.9

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Intradialytic Hypertension	Drug: Carvedilol vs. Prazosin

Study Design

Study Type:

Observational

Actual Enrollment :

76 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

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

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Apr 1, 2018

Actual Study Completion Date :

Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Carvedilol (for Aim 3 only) 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
Prazosin (for Aim 3 only) 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

Arm

Intervention/Treatment

Carvedilol (for Aim 3 only)

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

Prazosin (for Aim 3 only)

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

Outcome Measures

Primary Outcome Measures

Ratio of Extracellular Body Water to Total Body Water [Expected recruitment is 4-5 years]

Secondary Outcome Measures

Change in Endothelin-1 from pre to post dialysis [Expected recruitment is 4-5 years]

Other Outcome Measures

Change in Vascular Resistance from pre to post dialysis [Expected recruitment is 4-5 years]
Change in Asymmetric Dimethylarginine From pre to post dialysis [Expected recruitment is 4-5 years]
Change in Angiotensin II from pre to post dialysis [Expected recruitment is 4-5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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