Extravascular Lung Water Monitoring by Combined Ultrasound and Bioimpedance as a Guide for Treatment in Hemodialysis Patients (BUST)

Patients will be selected from the Dialisys Centers in Iasi, Romania. Patients will be randomized 1:1 to have a dry-weight assessment based on clinical (control) or lung US and bioimpedance (active) guided protocol. In the control group post-dialysis dry weight will be adjusted based on clinical criteria only (blood pressure, presence of edema, intradialytic hypotension, cramps etc.) and in the active group the target weight will be prescribed using lung US and bioimpedance evaluation.

In patients randomized to the active arm of the study, the US B-line score (BLS) will be measured before dialysis and these measurements will be used to titrate ultrafiltration prescription. In patients presenting moderate to severe lung congestion (≥15 BLS pre-dialysis) LUS measurements will be repeated once a week until the treatment goal was achieved (<15 BLS pre-dialysis) and once a month thereafter. The same (monthly) monitoring frequency will be adopted also in patients without pulmonary congestion at pre-dialysis baseline (<15 BLS). Furthermore, the use of the technique is allowed whenever its application is deemed useful to assume clinical decisions by attending physicians. Patients in the active arm of the study without evidence of lung congestion at baseline who developed pulmonary congestion (≥ 15 BLS) during the trial will received the same treatment contemplated for those with lung congestion at baseline during the trial. The treatment goal will be pursued by ultrafiltration intensification realized within the same HD schedule (3 sessions x 4 hours/week) or, if not tolerated, by extra-dialyses, according to individual tolerance and feasibility. In case of clinical hypovolemia (persistent cramps, hypotension etc) additional dry-weight adjustments will be performed according to the bioimpedance measurement, provided that the patients are below 15 BLS. This addition will be necessary in order to be able to increase the dry-weight in patients with a persistent BLS < 15 and avoid under perfusion.

Patients in the control arm of the study will be followed up and managed strictly with standard criteria according to current recommendations (implying optimization of fluids volume control on the basis of clinical criteria and the use of carvedilol, ACE inhibitors/sartans whenever deemed necessary); the use of lung US / bioimpedanc assistance will not be messured in these patients.

The main exclusion criteria will be the presence of severe cardiac failure (NYHA class III-IV), past myocardial infarction, stable or unstable angina and acute coronary syndrome. Due to bioimpedance assessment limitation patients with metallic joint prostheses, cardiac stent or pacemakers, decompensated cirrhosis, pregnancy and limb amputations will be excluded, as BIS cannot be accurately performed in such cases. Due to lung US measurement limitation we will exclude patients with known persistent pleurisy, pulmonary fibrosis or pneumectomy. Other exclusion criteria will be malignancy, active infections, temporary or permanent catheter as a vascular access, mental incompetence and unwillingness to participate in the study.

Study Overview

• Status: Completed
• Conditions: Patients on Hemodialysis for More Than 3 Months
• Intervention / Treatment: Other: Active arm

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Romania
  • Iasi, Romania, 700503
    • University Hospital "Dr. C.I. Parhon", Iasi, Department of Nephrology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• patients in hemodialysis for more than 3 months, that have no absolute contraindication for for performing bioimpedance measurements (amputation, stent, pregnancy, severe ascites) and ultrasound lung comets measurements (persistent pleuresia, pulmonary fibrosis, pneumectomy).

Exclusion Criteria:

• Patients with metallic joint prostheses, cardiac pacemakers, decompensated cirrhosis, limb amputations and severe conditions with life expectations <1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active arm of the study; The number of ultrasound lung comets (ULC) will directly adjust the prescribed post-hemodialysis dry weight. The US B-line score (BLS) will be measured before dialysis. In patients presenting moderate to severe lung congestion (≥15 BLS pre-dialysis) LUS measurements will be repeated once a week until the treatment goal was achieved (<15 BLS pre-dialysis) and once a month thereafter. monthly monitoring frequency will be adopted also in patients without pulmonary congestion (BLS <15). Patients without evidence of lung congestion at baseline who developed pulmonary congestion (≥ 15 BLS) during the trial will received the same treatment contemplated for those with lung congestion at baseline during the trial.	Other: Active arm; In the active arm of the study, the number of ultrasound lung comets (ULC) will directly adjust the prescribed post-hemodialysis dry weight. See study flowchart on page 1. If the patient does not tolerate the intervention (as described above), he will continue the study in the "medication arm", where the actual intervention in stopped, and extra cardio-protective drugs are added to the medication.
No Intervention: Standard care arm; In the control arm of the study, the dry weight will be assessed only clinically.Patients in the control arm of the study will be followed up and managed strictly with standard criteria according to current recommendations (implying optimization of fluids volume control on the basis of clinical criteria and the use of carvedilol, ACE inhibitors/sartans whenever deemed necessary); the use of lung US / bioimpedance assistance was not allowed in these patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Left ventricular mass measured by echocardiography	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume measures	bio-impedance (RXc graph, vector length, impedance ratio, phase angle, ECW:TBW ratio), weight, N-BNP, mean and pulse arterial pressure	2 years
Health-related quality of life (HRQOL)		2 years

Collaborators and Investigators

• Sponsor: Grigore T. Popa University of Medicine and Pharmacy
• Investigators: Principal Investigator: Adrian Covic, MD, PhD, FRCP, University of Medicine and Pharmacy "Gr. T. Popa", Iasi, Nephrology Department

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: March 19, 2013
• First Submitted That Met QC Criteria: March 20, 2013
• First Posted (Estimate): March 21, 2013

Study Record Updates

• Last Update Posted (Estimate): March 2, 2016
• Last Update Submitted That Met QC Criteria: March 1, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: mortality; hemodialysis; arterial stiffness; bioimpedance; overhydration
• Other Study ID Numbers: RandBCM