Ultrafiltration Profiling and Outcomes Among Individuals on Maintenance Hemodialysis

End Stage Renal Disease Clinical Trial

Official title:

Ultrafiltration Profiling and Outcomes Among Individuals on Maintenance Hemodialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03301740
• Other study ID #: 17-1057
• Secondary ID: 1K23DK109401
• Status: Completed
• Phase: N/A
• Start date: March 12, 2018
• Est. completion date: December 18, 2018

Study information

• Verified date: January 2019
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The rate of fluid removal (ultrafiltration, UF) during hemodialysis (HD) may contribute to cardiovascular morbidity and mortality among individuals receiving maintenance HD. More rapid UF rates are associated with higher morbidity and mortality. Ultrafiltration profiling, the practice of varying UF rates to maximize fluid removal during periods of greatest hydration and plasma oncotic pressures, is one treatment modification that may reduce UF-related harm without necessitating reduction in interdialytic fluid intake or longer HD treatments. To date, UF profiling has not been adequately studied independent of sodium profiling.

This study investigates the comparative effect of UF profiling versus non-profiled conventional HD on select cardiovascular and patient-reported outcomes. Participants will complete two phases of UF profiling and two phases of conventional HD and will act as their own controls.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 18, 2018
• Est. primary completion date: December 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• UF rate >10 mL/h/kg in >30% of treatments in a 30-day screening period (require =6 outpatient HD treatments in this period)

• Age 18-85 years

• Ability to converse comfortably in English or Spanish

• Receipt of in-center maintenance HD at Carolina Dialysis clinics in Carrboro or Siler City, North Carolina

• =90 days on HD

• Free of bloodstream infection during screening period

• Willingness to undergo all study testing

• Evidence of a signed and dated informed consent document

Exclusion Criteria:

• Systolic BP unable to be measured by arm cuff

• >1 hospitalization during screening period

• Unstable angina per treating nephrologist

• End-stage cirrhosis per treating nephrologist

• New York Heart Association class IV heart failure per treating nephrologist

• Pregnant

• More than 4 times per week HD

• Incarcerated

• Anticipated kidney transplant within 6 months per treating nephrologist

• Non-adherence to HD prescription (>2 unexplained absences during screening period)

• Sodium profiling or UF profiling in standard HD prescription

• Decisionally challenged, unable to provide informed consent

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Other:
• UF profiling during HD
Experimental arm: Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; pre-programmed "profile 2" on a Fresenius 2008K machine, the machine used in all participating clinics). Ultrafiltration profiling will be performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.
• Conventional HD
Control arm: Conventional HD (routine care) is the participant's standard HD prescription without UF profiling.

Locations

Country	Name	City	State
United States	Carolina Dialysis - Carrboro	Carrboro	North Carolina
United States	Carolina Dialysis - Siler City	Siler City	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of Intradialytic Hypotension (Intradialytic Hypotension Defined as Nadir Systolic BP <90 mmHg)	Intradialytic blood pressure (BP) was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Intradialytic hypotension was defined as the presence of a nadir systolic BP <90 mmHg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks
Primary	Pre- to Post-hemodialysis Treatment Change in Troponin T Level in ng/mL at Weeks 3, 7, 11, and 15, Using Mixed Model Analysis	Troponin T blood samples were collected at 4 study visits. Specifically, at the 7th hemodialysis treatment in each respective study phase (i.e., at week 3, 7, 11, and 15 study visits). Pre- to post-hemodialysis troponin T change was calculated as: post-dialysis troponin T - pre-dialysis troponin T (ng/mL). A lower change value reflects less cardiac strain. Based on the pre-specified protocol, the reported values represent change in troponin T between pre- and post-hemodialysis using mixed model (repeated measures logistic regression) analysis that considered all specified time-points (i.e., weeks 3, 7, 11, and 15).	Weeks 3, 7, 11, and 15
Primary	Occurrence of a =10% Troponin T Percentage Rise From Pre- to Post-hemodialysis Treatment	Troponin T blood samples were collected before and after each participant's 7th hemodialysis treatment of each study phase (4 times during the study). Troponin T percentage change was calculated as [(Post-HD troponin T - pre-HD troponin T) / pre-HD troponin T] x100. Troponin T percentage rise was defined as a troponin T percentage change =10%. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 3, 7, 11, and 15
Primary	Change From Baseline in Percent Left Ventricular Global Longitudinal Strain (GLS)	Left ventricular GLS was measured with transthoracic echocardiography at baseline and at 30 minutes before HD treatment end during the 7th treatment in the first phase of each arm. Left ventricular GLS change was calculated as peak intradialytic stress GLS - baseline GLS (%). A lower change value reflects lesser cardiac strain. Median differences were estimated using Wilcoxon (Mann-Whitney) tests.	Weeks 3 and 7
Secondary	Nadir Systolic Blood Pressure During Hemodialysis in mmHg	Intradialytic BP was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Nadir systolic BP was defined as the lowest intradialytic systolic BP measurement during each hemodialysis treatment. Lower values reflect greater cardiac strain. Beta-coefficients were estimated using a mixed model (repeated measures linear regression model).	Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks
Secondary	Occurrence of Failed Target Weight Achievement (Failed Target Weight Achievement Defined as a Difference in Prescribed Target Weight and Post-dialysis Weight That is >1 kg or <-1 kg)	The treating nephrologist prescribed the target weight per routine clinical care. Post-dialysis weight was measured after each hemodialysis treatment in the standing position, per dialysis clinic protocol. Failed target weight achievement was defined as a difference in prescribed target weight and post-dialysis weight that was >1 kg or <-1 kg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks
Secondary	Occurrence of Patient-reported Clinically Important Cramping During Dialysis (Clinically Important Cramping Defined as Moderate, Severe, or Very Severe Cramping)	Participants' dialysis-related symptoms (e.g. cramping) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important cramping was defined as cramping ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Nausea or Upset Stomach During Dialysis (Clinically Important Nausea or Upset Stomach Defined as Moderate, Severe, or Very Severe Nausea or Upset Stomach)	Participants' dialysis-related symptoms (e.g. nausea or upset stomach) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important nausea/upset stomach was defined as nausea/upset stomach ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Vomiting or Throwing up During Dialysis (Clinically Important Vomiting or Throwing up Defined as Moderate, Severe, or Very Severe Vomiting or Throwing up)	Participants' dialysis-related symptoms (e.g. vomiting or throwing up) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important vomiting/throwing up was defined as vomiting/throwing up ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Dizziness or Lightheadedness During Dialysis (Clinically Important Dizziness or Lightheadedness Defined as Moderate, Severe, or Very Severe Dizziness or Lightheadedness)	Participants' dialysis-related symptoms (e.g. dizziness or lightheadedness) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important dizziness/lightheadedness was defined as dizziness/lightheadedness ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Racing Heart or Heart Palpitations During Dialysis (Clinically Important Racing Heart or Heart Palpitations Defined as Moderate, Severe, or Very Severe Racing Heart or Heart Palpitations)	Participants' dialysis-related symptoms (e.g. racing heart or heart palpitations) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important racing heart/heart palpitations was defined as racing heart/heart palpitations ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Chest Pain During Dialysis (Clinically Important Chest Pain Defined as Moderate, Severe, or Very Severe Chest Pain)	Participants' dialysis-related symptoms (e.g. chest pain) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important chest pain was defined as chest pain ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Shortness of Breath During Dialysis (Clinically Important Shortness of Breath Defined as Moderate, Severe, or Very Severe Shortness of Breath)	Participants' dialysis-related symptoms (e.g. shortness of breath) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important shortness of breath was defined as shortness of breath ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Thirst or Dry Mouth During Dialysis (Clinically Important Thirst or Dry Mouth Defined as Moderate, Severe, or Very Severe Thirst or Dry Mouth)	Participants' dialysis-related symptoms (e.g. thirst or dry mouth) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important thirst/dry mouth was defined as thirst/dry mouth ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Headache During Dialysis (Clinically Important Headache Defined as Moderate, Severe, or Very Severe Headache)	Participants' dialysis-related symptoms (e.g. headache) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important headache was defined as headache ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Itching During Dialysis (Clinically Important Itching Defined as Moderate, Severe, or Very Severe Itching)	Participants' dialysis-related symptoms (e.g. itching) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important itching was defined as itching ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Restless Legs During Dialysis (Clinically Important Restless Legs Defined as Moderate, Severe, or Very Severe Restless Legs)	Participants' dialysis-related symptoms (e.g. restless legs) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important restless legs was defined as restless legs ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
Secondary	Occurrence of Patient-reported Clinically Important Tingling or Feeling of Pins and Needles During Dialysis (Clinically Important Tingling or Feeling of Pins and Needles Defined as Moderate, Severe, or Very Severe Tingling or Feeling of Pins and Needles)	Participants' dialysis-related symptoms (e.g. tingling or feeling of pins and needles during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important tingling/feeling of pins and needles was defined as tingling/feeling of pins and needles ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).	Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15