Conventional Hemodialysis vs. Short Daily Hemodialysis (6 Days / Week) and Mechanisms of Blood Pressure Control

End Stage Renal Disease Clinical Trial

Official title:

Randomized Cross-over Study of Short Daily Hemodialysis Compared to Conventional Hemodialysis to Determine the Mechanisms of Hypertension Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00759967
• Other study ID #: 2006 77401H
• Status: Completed
• Phase: Phase 3
• First received: September 24, 2008
• Last updated: July 11, 2012
• Start date: September 2007
• Est. completion date: June 2012

Study information

• Verified date: July 2012
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

More than 80% of patients with end stage renal disease have hypertension; 70% of whom are poorly controlled using conventional Hemodialysis therapy. An expanded extracellular fluid volume and an increase in peripheral vascular resistance as a result of hemodynamic/trophic effects of an increased sympathetic nerve activity, angiotensin II, asymmetrical dimethyl arginine, and decreased nitric oxide are the most frequently quoted mechanisms contributing to hypertension in this population. The intermittent nature of conventional hemodialysis treatments (4 hours, 3 days/week) results in the majority of patients having a sustained expansion of the extracellular fluid volume that likely contributes to the activation of neurohormonal pathways. However, daily therapy including short daily hemodialysis (2 hours, 6 days/week) and nocturnal hemodialysis (6-8 hours, 5-6 days/week) improve or even normalize blood pressure. Short daily hemodialysis appears to improve blood pressure secondary to a reduction in extracellular fluid volume (7,8) whereas the improvement in blood pressure with nocturnal hemodialysis occurs by a reduction in peripheral vascular resistance (8,9,10). This is consistent with the Katzarski et al experience (7-8 hours, 3 days/week) and one randomized controlled trial in which blood pressure control was due to normalization of extracellular fluid volume in some patients and a reduction in peripheral vascular resistance in others. The majority of the studies in daily dialysis are observational, do not include a run-in period to optimize blood pressure management and have not explored the mechanisms of improvement in blood pressure in detail. We have designed a 9 month study to determine if the mechanism by which short daily hemodialysis is associated with an improvement in blood pressure control is secondary to changes in sympathetic nervous system activity and/ or extracellular fluid volume. Additionally we would like to explore the potential impact of short daily dialysis, compared to conventional dialysis, on markers of inflammation and oxidative stress in detail.

Description:

Patients with end stage renal disease have an adjusted risk of cardiovascular mortality that is 10-20 times greater than the general population. Of the modifiable risk factors, hypertension occurs in 80% of patients with end stage renal disease and is poorly controlled in 70% of patients. In several observational studies of daily hemodialysis, blood pressure has improved despite a reduction in the number of antihypertensive medications. A randomized crossover study in short daily hemodialysis also showed an improvement in systolic blood pressure and a reduction in left ventricular mass index. In limited investigation, the mechanism(s) responsible for the improvement in blood pressure have been attributed to a reduction in extracellular fluid volume (short daily) and a reduction in peripheral vascular resistance (nocturnal hemodialysis). The studies to date have been limited by failing to include a run in phase to optimize extracellular fluid volume prior to the initiation of daily dialysis. Additionally, only one study used a standardized algorithm for the management of blood pressure which is vital as the treatments are not blinded. We have designed a randomized, unblinded, 9 month cross-over study to determine the mechanism of blood pressure control on patients receiving conventional (3 times /week) HD to short daily HD (6 times /week 2 hrs/tx). After completing a 3 month run-in phase on conventional HD in which patient's dry weight and antihypertensive medications will be adjusted using a standardized algorithm, patients are to be randomized to a 3 month cross-over of daily HD versus conventional HD. The mechanism of improved blood pressure control will be explored using bioelectrical impedance to measure extracellular fluid volume (ECFV) and muscle sympathetic nerve activity (MSNA) as well as plasma catecholamines to measure the activity of the sympathetic nervous system. Additionally the effect of short daily HD, compared to conventional HD, on reactive oxygen species and markers of inflammation will be examined in Dr. Rhian Touyz lab. Lastly we will determine the patient's treatment preference.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: June 2012
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Systolic Hypertension

• They are able to make the time commitment for daily therapy

• They are capable of giving informed consent.

Exclusion Criteria:

• They are expected to receive a transplant within the next 12 months

• If they are considering a switch to peritoneal dialysis

• They are not expected to survive 12 months

• They have infections that require isolation (Vancomycin Resistant Enterococcus, Methicillin Resistant Staphylococcus Aureus, Hepatitis B)

• They have known symptomatic dilated cardiomyopathy (New York Association Class II or III with left ventricle ejection fraction of <0.35

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic

Intervention

Procedure:
• Microneurography
Muscle sympathetic nerve activity measurement will be obtained using microneurography. Approximately 10-20% of microneurography recordings are not interpretable due to technical problems. For this reason, blood samples will be collected at the same time that the microneurography is to be done. These test will be done at 3 time points throughout the study.
• Bioimpedance testing
bioimpedance measurement of extracellular fluid volume will be measured at the end of each 3 month period. This test will be done at 3 time points throughout the study.

Locations

Country	Name	City	State
Canada	The Ottawa Hospital	Ottawa	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Heart and Stroke Foundation of Ontario, University of Ottawa

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BP measured by the average of 2 measurements, pre and post dialysis in accordance with guidelines form Canadian Hypertension Society	To determine if short daily hemodialysis , compared to conventional hemodialysis, is associated with a sustained (> 3months) improvement in systolic blood pressure.	two years	No
Secondary	To determine if the mechanism by which short daily hemodialysis is associated with an improvement in blood pressure control is secondary to changes in sympathetic nervous system and/ or extracellular fluid volume	extracellular fluid volume will be measured using bioelectrical impedance, sympathetic nervous system activity using microneurography and plasma catecholamines	once the final participant has completed all study procedures	No
Secondary	To determine if short daily hemodialysis, compared to conventional hemodialysis maintains metabolic homeostasis (serum calcium, phosphate, potassium and bicarbonate)		once the last participant has completed all study procedures	No
Secondary	To determine if the enhance control of blood pressure with daily hemodialysis compare to conventional hemodialysis is associated with a reduction in oxidative stress and markers of inflammation.		once the final participant has completed all study procedures	No
Secondary	To determine patient modality preference.	each participant will complete a questionair regarding modality preference	at study completion	No