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

NCT00759967 | Completed Results DMC

• 1 other identifier: 2006 77401H
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

End Stage Renal Disease

Keywords

Randomized; Cross-Over; Conventional; Daily; Hemodialysis

Outcome Measures

Primary Outcomes (1)

• Mean Systolic Blood Pressure Over the Third Month of Each Treatment Arm

  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

  Average of the last month of the 3 month intervention

Secondary Outcomes (5)

• To Determine if the Mechanism by Which Short Daily Hemodialysis is Associated With Changes in Extracellular Fluid Volume

  once the final participant has completed all intervention procedures, approx. 3 months

• To Determine if Short Daily Hemodialysis, Compared to Conventional Hemodialysis Maintains Metabolic Homeostasis

  once the last participant has completed run in phase and after randomization, approx. 3 months

• To Determine if the Enhance Control of Blood Pressure With Daily Hemodialysis Compare to Conventional Hemodialysis is Associated With a Reduction in Oxidative Stress.

  once the final participant has completed all intervention procedures, approx. 3 months

• To Determine Patient Modality Preference.

  at study completion

• 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

  once the final participant has completed all intervention procedures, approx. 3 months

Study Arms (2)

Short daily hemodialysis

ACTIVE COMPARATOR

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; Procedure: Bioimpedance testing

Conventional hemodialysis

ACTIVE COMPARATOR

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; Procedure: Bioimpedance testing

Interventions

Microneurography PROCEDURE

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.

Also known as: Catecholamines

Conventional hemodialysis; Short daily hemodialysis

Bioimpedance testing PROCEDURE

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.

Also known as: Bioimpedance, extracellular fluid volume measurement

Conventional hemodialysis; Short daily hemodialysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Systolic Hypertension
• They are able to make the time commitment for daily therapy
• They are capable of giving informed consent.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Heart and Stroke Foundation of Ontario: collaborator
• University of Ottawa: collaborator

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1H 7W9, Canada

Location

Related Publications (1)

• 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.

  PMID: 24875804 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Catecholamines

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

Although 2 patients stopped doing short daily HD they were included in the intention to treat analysis with their short daily HD BPs carried forward

Results Point of Contact

• Title: Dr. Deborah Zimmerman
• Organization: Ottawa Hospital Research Institute

dzimmerman@ohri.ca

613-738-8400

Study Officials

• Deborah Zimmerman, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2008
• First Posted: September 25, 2008
• Study Start: September 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2012
• Last Updated: August 4, 2017
• Results First Posted: August 4, 2017

Record last verified: 2017-01

Locations

CA (1)