Adjusting Fluid Removal Based on Blood Volume in Hemodialysis: A Randomized Study

Study Overview
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Brief Summary
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As kidney function declines, the ability to maintain water balance is impaired and is most often treated with hemodialysis. The removal of excess water in hemodialysis often leads to a sudden drop of blood pressure and causes symptoms of dizziness, light-headedness, cramping, and chest pain. This sudden drop in blood pressure has been linked with complications of heart attacks, strokes and even death. Research has focused on different ways to prevent dangerous drops in blood pressure during hemodialysis. One way is the use of blood volume monitoring biofeedback technology to monitor the patient's relative blood volume and automatically reduce the amount of fluid that is being removed when the blood volume is low to prevent the drop in blood pressure from occurring. This type of biofeedback device is currently available on some hemodialysis machines and while this approach appealing, it is not clear how effective this form of biofeedback is in preventing the drops in blood pressure. We plan to determine if the use of biofeedback based on the changes in the patient's blood volume will reduce the number of sudden drops in blood pressure that occur during hemodialysis. To do this, we will compare patients treated with this technology to current hemodialysis practices and follow them for important adverse outcomes. The result of interest will be the frequency of hemodialysis sessions complicated by a sudden symptomatic drop in blood pressure. We also plan to monitor the amount of water in the different body compartments, blood pressure, blood pressure medication use, markers of heart function, and patient symptoms and quality of life. We hope that by providing information on this technology we can reduce the sudden drops in blood pressure in hemodialysis, the associated rates of serious disease or death, and improve patient quality of life.

Detailed Description
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This is a 22 week parallel group, randomized crossover trial to determine the effect of blood volume monitoring, BVM, guided ultrafiltration (UF) biofeedback on symptomatic intradialytic hypotension (IDH) episodes amongst IDH prone patients. The first part of the study (Part 1 - Run-In/Dialysis Optimization Phase), eligible patients will undergo a four-week run-in phase. During this period all patients will undergo a comprehensive clinical assessment including, clinical weight assessment, anti-hypertensive medication review, and dialysis prescription standardization. At the end of the run-in phase, patients that still meet eligibility criteria will enter the randomized cross-over phase. In part 2 (Randomized Cross-Over Phase), patients are randomized to regular best clinical practice hemodialysis, HD (without BVM-guided UF biofeedback; control arm) or to BVM-guided UF biofeedback (intervention arm) for an 8 week period. This will be followed by a two-week washout phase and then patients will be crossed over for a second 8-week phase. The study will be conducted and reported following the Consolidated Standards of Reporting Trials (CONSORT) 2010 guidelines.

Official Title
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Blood Volume Monitoring Guided Ultrafiltration Biofeedback on Reduction of Intra-dialytic Hypotensive Episodes in Hemodialysis: A Randomized Cross Over Study

Conditions
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Intradialytic Hypotension, End Stage Renal Failure on Dialysis

Intervention / Treatment
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* Device: BVM-UF biofeedback
* Device: Fresenius 5008 HD machine (Fresenius Medical Care, Bad Homburg, Germany)


Participation Criteria
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Eligibility Criteria
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Run-in Phase Inclusion Criteria: >18 years old Maintenance hemodialysis patients for more than 3 months Undergo hemodialysis 3-4 times per week for a minimum of three hours per session Have >30% of their hemodialysis sessions in the preceding 8 weeks complicated by symptomatic IDH. Able to provide written informed consent. Randomization Phase Inclusion Criteria: >18 years old Maintenance hemodialysis patients for more than 3 months Undergo hemodialysis 3-4 times per week for a minimum of three hours per session Have >30% of their hemodialysis sessions in the preceding 4 weeks complicated by symptomatic IDH. Exclusion Criteria: Serum sodium ≤133mmol/L Hemoglobin <80g/L Active Malignancy History of blood transfusions or hospitalizations in the preceding 4 weeks Planned change in the renal replacement modality during the planned study period

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Best clinical practice HD<br>All study patients will be dialyzed with the Fresenius 5008 HD machine (Fresenius Medical Care, Bad Homburg, Germany) using high flux dialyzers. For an 8-week period, patients in the best clinical practice (control) phase will use their same prescription as the run-in phase, dialysate sodium of 138mmol/L, dialysate calcium of 1.25mmol/L, dialysate temperature of 36oC, and constant UF rate. BVM will be disabled in this group. | Device: Fresenius 5008 HD machine (Fresenius Medical Care, Bad Homburg, Germany)<br>* For an 8-week period, patients in the best clinical practice (control) phase will use their same prescription as the run-in phase, dialysate sodium of 138mmol/L, dialysate calcium of 1.25mmol/L, dialysate temperature of 36oC, and constant UF rate. BVM will be disabled in this group.<br>|
| Experimental: Best clinical practice plus BVM-guided UF biofeedback<br>Patients in the BVM-guided UF biofeedback (intervention) phase will have the same prescription as the control group but will also have the ultrafiltration rate automatically adjusted by the Fresenius 5008 HD machine based on the changes in the relative blood volume. | Device: BVM-UF biofeedback<br>* The Fresenius 5008 uses an ultrasound and temperature monitor incorporated into the machine to detect ultrasonic velocity and temperature changes to derive the total protein concentration, which is a sum of total plasma proteins and hemoglobin. The relative blood volume is calculated at by dividing the initial concentration of total protein by the total protein concentration at any given time, multiplied by 100. The HD software is based on the critical blood volume entered at the beginning of the dialysis session for each individual patient. The UF rate is adjusted based on the changes in the relative blood volume to the patient's critical relative blood volume.<br>* Other names: Fresenius 5008 HD machine with UF control;Device: Fresenius 5008 HD machine (Fresenius Medical Care, Bad Homburg, Germany)<br>* For an 8-week period, patients in the best clinical practice (control) phase will use their same prescription as the run-in phase, dialysate sodium of 138mmol/L, dialysate calcium of 1.25mmol/L, dialysate temperature of 36oC, and constant UF rate. BVM will be disabled in this group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the rate of symptomatic IDH during hemodialysis | The primary outcome will be rate of symptomatic IDH as defined by an abrupt drop in the systolic blood pressure of ≥20mm Hg when compared to baseline along with an abrupt onset headache, dizziness, unconsciousness, thirst, dyspnea, angina, muscle cramps, or vomiting (reflecting cerebral, cardiac, gastrointestinal, or musculoskeletal ischemia). The end of an episode of IDH will be defined as resolution of the symptom. The number of symptomatic IDH episodes along with the duration of each dialysis treatment will be captured. The rate of IDH for each session will be calculated by dividing the number of episodes by the duration of the session in hours. The rate of IDH will be calculated for every dialysis treatment. The rate of symptomatic IDH will be measured in the two months preceding enrollment, during each phase of the study. | During hemodialysis up to the 22 week study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the number of symptomatic IDH per dialysis session | The number of symptomatic IDH episodes in each dialysis treatment will be captured. IDH is defined as in the primary outcome. | During hemodialysis up to the 22 week study period | 
| Change in the frequency of symptomatic IDH | The number of symptomatic IDH episodes of each dialysis treatment will be captured. IDH is defined as in the primary outcome. | During hemodialysis up to the 22 week study period | 
| Number and Frequency of Nursing Interventions during hemodialysis | IDH-related nursing interventions are defined as the use of Trendelenburg/supine position, discontinuation of UF, fluid/saline challenge, return of blood, shortened dialysis run, or prolonged (more than 15 minutes) post-dialysis recovery period as a result of IDH or its symptoms. Given the subjective nature of IDH-related symptoms and intervention, in-services and customized dialysis run sheets will be provided to all nurses at participating dialysis centers to ensure that all events are recorded and recorded consistently. The number of symptomatic IDH episodes per session will be record. | During hemodialysis up to the 22 week study period | 
| Change in Single Session Dialysis Adequacy | Patients that experience symptomatic IDH may require a reduction in the duration of HD treatments with a resultant reduction in dialysis adequacy. Dialysis adequacy will be measured and recorded (usual care) at the end of each dialysis session on the session sheet as single-pooled Kt/V. Single-pooled Kt/v is measured using the previously validated online clearance measurement method, which detects changes in conductivity in the dialysate to reflect the clearance of serum electrolytes and urea. | After hemodialysis up to the 22 week study period | 
| Electrical Bio-impedance for the determination of change in hydration and fluid status | Whole body and segmental bio-impedance analysis for the determination of fluid composition has been validated in HD patients. Improvement of dry weight has been linked with reduced mortality. Electrical bio-impedance will be performed at the end of the mid-week HD session at week 1, 4, 8, 12, 14, 18, and 22 to determine the total body water, extracellular fluid volume (ECFV), intracellular fluid volume (ICFV), and the ECFV:ICFV ratio. | At the end of the mid-week HD session at week 1, 4, 8, 12, 14, 18, and 22. Up to week 22 study period. | 
| Change in Serum Brain Natriuretic Peptide (BNP) | Chronic hypervolemia in HD is associated with increase in left atrial volume and BNP, which has been shown to predict mortality. Serum BNP will be measured at the beginning of the mid-week HD session at week 1, 4, 12, 14, and 22. | At the beginning of the mid-week HD session at week 1, 4, 12, 14, and 22. Up to week 22 study period. | 
| Change in Serum high sensitivity cardiac troponin (hs-Troponin) | Biomarkers of cardiac damage such as hs-Troponin are more elevated in HD patients with myocardial stunning and is associated with an increased all-cause mortality. Improved and more frequent dialysis has been associated with a decrease in myocardial stunning, and a trend towards decreasing hs-troponin. Serum hs-Troponin will be performed at the beginning of the mid-week HD session at week 1, 4, 12, 14, and 22. | At the beginning of the mid-week HD session at week 1, 4, 12, 14, and 22. Up to week 22 study period. | 
| Change in antihypertensive medication use | Improvements in a patient's volume status and blood pressure allows for a decrease number or dose of anti-hypertensive medications. The class and number of anti-hypertensive medications will be obtained from the electronic clinical database and subsequently confirmed with a patient interview at enrollment and the mid-week HD session at week 4, 8, 12, 14, 18, and 22. The study investigator will perform medication reconciliation | At enrollment and the mid-week HD session at week 4, 8, 12, 14, 18, and 22. | 
| Relative blood volume Curve | The shape and slope of the RBV curve has been associated with symptomatic hypotensive episodes in HD. The relative blood volume curve will be downloaded from the Fresenius 5008 dialysis machine to a study computer on a regular basis for all patients in the run-in phase and those in the intervention arm following randomization. The relative blood volume achieved, maximum slope (%/h) of the BVM curve as defined by the percent (%) decline over time (h) will be calculated. The subjective pattern of BVM curve (flat, linear, concave upward, concave downward, regular and irregular line will be determined by the study investigator. | After every hemodialysis session, up to the 22 week study period. | 
| Improvement in Intra-dialytic symptom survey | Currently no validated intra-dialytic symptom survey exists to provide an objective measure of intra-dialytic symptom burden. The survey will inquire about the intra-dialytic symptoms of IDH, specifically nausea, vomiting, chest pain, shortness of breath, headache, muscle cramps, dizziness, fainting, fatigue, and anxiety. The survey will be provided by the dialysis nurse, and to be completed by the patient or in conjunction with the dialysis nurse at the end of the dialysis session during weeks 1, 4, 8, 12, 14, 18, and 22. The survey is expected to take less than 1 minute to complete. | At the end of each dialysis session, during weeks 1, 4, 8, 12, 14, 18, and 22. Up to the 22 week study period. | 
| Improvement in Inter-dialytic symptom survey | A survey inquiring about inter-dialytic recovery time to baseline will be provided by the dialysis nurse, and to be completed by the patient or in conjunction with the dialysis nurse at the beginning of dialysis during weeks 1, 4, 8, 12, 14, 18, and 22. The survey will inquire the time it took the patient to recovery from the last dialysis session, is validated in HD patients as a robust assessment quality of life. The survey will take less than 30 seconds to complete. | At the beginning of each dialysis session, during weeks 1, 4, 8, 12, 14, 18, and 22. Up to the 22 week study period. | 
| Assessment of Nursing Perception, Attitudes, and Satisfaction of BVM guided UF biofeedback system | A survey inquiring about nursing perception and attitudes of the BVM guided UF biofeedback will be provided to the nurses at the end of the control and intervention phase. The survey is developed for the purpose of this study. | At the end of the control and intervention phase (end of week 12 and 22). Up to the 22 week study period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intradialytic Hypotension, Renal Dialysis, Blood Volume Determination, Clinical Trials, Randomized, Crossover Studies