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

• ClinicalTrials.gov Identifier: NCT00759967
• Recruitment Status: Completed
• First Posted: September 25, 2008
• Results First Posted: August 4, 2017
• Last Update Posted: August 4, 2017
• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Heart and Stroke Foundation of Ontario; University of Ottawa
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
End Stage Renal Disease	Procedure: Microneurography; Procedure: Bioimpedance testing	Not Applicable

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Cross-over Study of Short Daily Hemodialysis Compared to Conventional Hemodialysis to Determine the Mechanisms of Hypertension Control
• Study Start Date: September 2007
• Actual Primary Completion Date: June 2011
• Actual Study Completion Date: June 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Short daily hemodialysis; After a 3 month run-in period patients who are randomized to this arm will receive 3 months of short daily hemodialysis(2 hours/day,6 days/week)B/P will be monitored according to the Canadian hypertension guidelines both pre and post each dialysis session. Antihypertensive medication will be adjusted accordingly to maintain BP within the guidelines.At the end of this 3 month period extracellular fluid volume (bioimpedance) will be measured using bioimpedance as well as sympathetic nerve activity using microneurography. Additionally Catecholamines as well as markers of oxidative stress will be collected.	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.; Other Name: Catecholamines; Procedure: 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.; Other Names: Bioimpedance; extracellular fluid volume measurement
Active Comparator: Conventional hemodialysis; After a 3 month run-in period patients who are randomized to this arm will receive 3 months of conventional hemodialysis 3 days/week 3.5-4 hours/ treatment. BP will be monitored according to the Canadian hypertension guidelines both pre and post each dialysis session. Antihypertensive medication will be adjusted accordingly to maintain BP within the guidelines.At the end of this 3 moth period extracellular fluid volume (bioimpedance) will be measured using bioimpedance as well as sympathetic nerve activity using microneurography. Additionally Catecholamines as well as markers of oxidative stress will be collected.	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.; Other Name: Catecholamines; Procedure: 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.; Other Names: Bioimpedance; extracellular fluid volume measurement

Outcome Measures

Primary Outcome Measures :

1. Mean Systolic Blood Pressure Over the Third Month of Each Treatment Arm [ Time Frame: Average of the last month of the 3 month intervention ]
   The average of 2 measurements taken pre each dialysis session in the third month of treatment were compared when the patients were on conventional hemodialysis compared to short daily hemodialysis. SBP was taken in accordance with guidelines from the Canadian Hypertension Society

Secondary Outcome Measures :

1. To Determine if the Mechanism by Which Short Daily Hemodialysis is Associated With Changes in Extracellular Fluid Volume [ Time Frame: once the final participant has completed all intervention procedures, approx. 3 months ]
   The extracellular fluid volume will be measured using bioelectrical impedance to determine if the mechanism by which short daily hemodialysis is associated with an improvement in blood pressure control is secondary to changes in extracellular fluid volume.
2. To Determine if Short Daily Hemodialysis, Compared to Conventional Hemodialysis Maintains Metabolic Homeostasis [ Time Frame: once the last participant has completed run in phase and after randomization, approx. 3 months ]
   Serum phosphate values from the end of the three month run in phase and after randomization used to measure metabolic homeostasis
3. To Determine if the Enhance Control of Blood Pressure With Daily Hemodialysis Compare to Conventional Hemodialysis is Associated With a Reduction in Oxidative Stress. [ Time Frame: once the final participant has completed all intervention procedures, approx. 3 months ]
4. To Determine Patient Modality Preference. [ Time Frame: at study completion ]
   each participant will complete a questionaire regarding modality preference
5. To Determine if the Enhance Control of Blood Pressure With Daily Hemodialysis Compare to Conventional Hemodialysis is Associated With a Reduction in Markers of Inflammation [ Time Frame: once the final participant has completed all intervention procedures, approx. 3 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

The Ottawa Hospital

Ottawa, Ontario, Canada, K1H 7W9

Sponsors and Collaborators

Ottawa Hospital Research Institute

Heart and Stroke Foundation of Ontario

University of Ottawa

Investigators

• Principal Investigator: Deborah Zimmerman, MD; Ottawa Hospital Research Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zimmerman DL, Ruzicka M, Hebert P, Fergusson D, Touyz RM, Burns KD. Short daily versus conventional hemodialysis for hypertensive patients: a randomized cross-over study. PLoS One. 2014 May 29;9(5):e97135. doi: 10.1371/journal.pone.0097135. eCollection 2014.

• Responsible Party: Ottawa Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT00759967
• Other Study ID Numbers: 2006 77401H
• First Posted: September 25, 2008
• Results First Posted: August 4, 2017
• Last Update Posted: August 4, 2017
• Last Verified: January 2017

Keywords provided by Ottawa Hospital Research Institute:

Randomized; Cross-Over; Conventional; Daily; Hemodialysis

Additional relevant MeSH terms:

Kidney Failure, Chronic; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency