Body Composition Monitor(BCM) Guided Fluid Management in Maintenance Hemodialysis (MHD) Patients (BOCOMO)

• Change from baseline in Left ventricular thickness once a year [ Time Frame: baseline, and once a year during the following 36 months ] [ Designated as safety issue: No ]
• Change from baseline in Pre-dialysis blood pressure every 2 months [ Time Frame: baseline, every 2 months during the following 36 months ] [ Designated as safety issue: No ]
• Change from baseline in anti-hypertensives DDD every 2 months [ Time Frame: Baseline, and every 2 months during the following 36 months ] [ Designated as safety issue: No ]
  Defined daily dose (DDD) will be calculated according to WHO recommendation at baseline, and every 2 months thereafter. Trend of DDD change will be compared between the two arms.
• Incidence of all cause and congestive heart failure related hospitalization [ Time Frame: during the 36 months ] [ Designated as safety issue: No ]
  Incidence of all cause and congestive heart failure related hospitalization will be compared between arms.

• Change from baseline in Left ventricular thickness once a year [ Time Frame: baseline, and once a year during the following 30 months ] [ Designated as safety issue: No ]
• Change from baseline in Pre-dialysis blood pressure every 2 months [ Time Frame: baseline, every 2 months during the following 30 months ] [ Designated as safety issue: No ]
• Change from baseline in anti-hypertensives DDD every 2 months [ Time Frame: Baseline, and every 2 months during the following 30 months ] [ Designated as safety issue: No ]
  Defined daily dose (DDD) will be calculated according to WHO recommendation at baseline, and every 2 months thereafter. Trend of DDD change will be compared between the two arms.
• Incidence of all cause and congestive heart failure related hospitalization [ Time Frame: during the 30 months ] [ Designated as safety issue: No ]
  Incidence of all cause and congestive heart failure related hospitalization will be compared between arms.

It is hypothesized that bioimpedance spectroscope guided fluid management will help patient reach euvolemic status, and increase long term survival.

Background: Bioimpedance analysis (BIA) was helpful in identifying hypervolemia. Observational data using BIA methods showed that hypervolemic patients on maintenance hemodialysis (MHD) suffered from high mortality risk. But it is not clear if BIA guided fluid management can improve MHD patients' survival. The objectives of the BOCOMO study are to evaluate the outcome of BIA guided fluid management comparing with standard care.

Design: This is a multicenter, prospective, randomized, controlled trial. Setting and Participants: More than 1300 participants from 16 clinical sites will be included in the study. The enrollment period will last 6 months, and minimum length of follow-up will not less than 36 months. MHD patients aged more than 18 years but less than 80 years who had been on MHD for at least 3 months and considered suitable candidates will be invited to participate in the study. Participants will be randomized to BIA arm or control arm using 1:1 ratio. A portable whole body bioimpedance spectroscopy device (BCM—Fresenius Medical Care D GmbH) will be used for BIA measurement at baseline for both arm, and every 2 months in BCM arm.

Predictors: BCM guided fluid management and fluid management using standard care.

Outcome and measurements: The primary intent-to-treat analysis compares composite endpoint between BCM arm and control arm. The secondary intent-to-treat analysis compares left ventricular thickness, blood pressure, medication, and incidence and length of hospitalization between BCM arm and control arm. Death, acute myocardial infarction, stroke, peripheral arterial disease will be used as composite endpoint.

• Device: body bioimpedance spectroscopy device
  Name of the device is BCM from Fresenius Medical Care D GmbH
• Device: Device
  participants in control arm will not receive BCM measurement.

• Experimental: BCM Arm
  BCM measured every 2 months
  Intervention: Device: body bioimpedance spectroscopy device
• Sham Comparator: Control arm
  patients care according to standard of care
  Intervention: Device: Device

• Wizemann V, Wabel P, Chamney P, Zaluska W, Moissl U, Rode C, Malecka-Masalska T, Marcelli D. The mortality risk of overhydration in haemodialysis patients. Nephrol Dial Transplant. 2009 May;24(5):1574-9. Epub 2009 Jan 7.
• Jansen MA, Hart AA, Korevaar JC, Dekker FW, Boeschoten EW, Krediet RT; NECOSAD Study Group. Predictors of the rate of decline of residual renal function in incident dialysis patients. Kidney Int. 2002 Sep;62(3):1046-53.
• Puskar D, Pasini J, Savi? I, Bedalov G, Sonicki Z. Survival of primary arteriovenous fistula in 463 patients on chronic hemodialysis. Croat Med J. 2002 Jun;43(3):306-11.
• Mizumasa T, Hirakata H, Yoshimitsu T, Hirakata E, Kubo M, Kashiwagi M, Tanaka H, Kanai H, Fujimi S, Iida M. Dialysis-related hypotension as a cause of progressive frontal lobe atrophy in chronic hemodialysis patients: a 3-year prospective study. Nephron Clin Pract. 2004;97(1):c23-30.
• John AS, Tuerff SD, Kerstein MD. Nonocclusive mesenteric infarction in hemodialysis patients. J Am Coll Surg. 2000 Jan;190(1):84-8.
• Shoji T, Tsubakihara Y, Fujii M, Imai E. Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients. Kidney Int. 2004 Sep;66(3):1212-20.
• Tislér A, Akócsi K, Hárshegyi I, Varga G, Ferenczi S, Grosz M, Kulcsár I, Löcsey L, Sámik J, Solt I, Szegedi J, Tóth E, Wágner G, Kiss I. Comparison of dialysis and clinical characteristics of patients with frequent and occasional hemodialysis-associated hypotension. Kidney Blood Press Res. 2002;25(2):97-102.
• Pillon L, Piccoli A, Lowrie EG, Lazarus JM, Chertow GM. Vector length as a proxy for the adequacy of ultrafiltration in hemodialysis. Kidney Int. 2004 Sep;66(3):1266-71.
• Movilli E, Gaggia P, Zubani R, Camerini C, Vizzardi V, Parrinello G, Savoldi S, Fischer MS, Londrino F, Cancarini G. Association between high ultrafiltration rates and mortality in uraemic patients on regular haemodialysis. A 5-year prospective observational multicentre study. Nephrol Dial Transplant. 2007 Dec;22(12):3547-52. Epub 2007 Sep 21.
• Chamney PW, Krämer M, Rode C, Kleinekofort W, Wizemann V. A new technique for establishing dry weight in hemodialysis patients via whole body bioimpedance. Kidney Int. 2002 Jun;61(6):2250-8.
• Ozkahya M, Ok E, Toz H, Asci G, Duman S, Basci A, Kose T, Dorhout Mees EJ. Long-term survival rates in haemodialysis patients treated with strict volume control. Nephrol Dial Transplant. 2006 Dec;21(12):3506-13. Epub 2006 Sep 25.
• Agarwal R, Alborzi P, Satyan S, Light RP. Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial. Hypertension. 2009 Mar;53(3):500-7. Epub 2009 Jan 19.
• Charra B. Fluid balance, dry weight, and blood pressure in dialysis. Hemodial Int. 2007 Jan;11(1):21-31. Review.
• Moissl UM, Wabel P, Chamney PW, Bosaeus I, Levin NW, Bosy-Westphal A, Korth O, Müller MJ, Ellegård L, Malmros V, Kaitwatcharachai C, Kuhlmann MK, Zhu F, Fuller NJ. Body fluid volume determination via body composition spectroscopy in health and disease. Physiol Meas. 2006 Sep;27(9):921-33. Epub 2006 Jul 25.
• van den Ham EC, Kooman JP, Christiaans MH, Nieman FH, Van Kreel BK, Heidendal GA, Van Hooff JP. Body composition in renal transplant patients: bioimpedance analysis compared to isotope dilution, dual energy X-ray absorptiometry, and anthropometry. J Am Soc Nephrol. 1999 May;10(5):1067-79.
• McClanahan BS, Stockton MB, Lanctot JQ, Relyea G, Klesges RC, Slawson DL, Schilling LP. Measurement of body composition in 8-10-year-old African-American girls: a comparison of dual-energy X-ray absorptiometry and foot-to-foot bioimpedance methods. Int J Pediatr Obes. 2009;4(4):389-96.
• Lintsi M, Kaarma H, Kull I. Comparison of hand-to-hand bioimpedance and anthropometry equations versus dual-energy X-ray absorptiometry for the assessment of body fat percentage in 17-18-year-old conscripts. Clin Physiol Funct Imaging. 2004 Mar;24(2):85-90.
• Kraemer M. A new model for the determination of fluid status and body composition from bioimpedance measurements. Physiol Meas. 2006 Sep;27(9):901-19. Epub 2006 Jul 24.
• Guida B, De Nicola L, Trio R, Pecoraro P, Iodice C, Memoli B. Comparison of vector and conventional bioelectrical impedance analysis in the optimal dry weight prescription in hemodialysis. Am J Nephrol. 2000 Jul-Aug;20(4):311-8.
• Liu L, Long G, Ren J, Li J, Xu J, Lei J, Li M, Qiu M, Yuan P, Sun W, Lin S, Liu W, Sun Y, Ma Y, Mao Y, Shen Y, Zuo L. A randomized controlled trial of long term effect of BCM guided fluid management in MHD patients (BOCOMO study): rationales and study design. BMC Nephrol. 2012 Sep 25;13:120. doi: 10.1186/1471-2369-13-120.

Inclusion Criteria:

• diagnosis of end stage renal disease (ESRD) and need MHD
• age of 18 years or older but 80 years or less
• on MHD for at least 3 months
• dialysis frequency of at least 5 sessions per 2 weeks, not less than 4 hours per session, Kt/V at least 1.2
• urine volume less than 800mL per 24 hours the day before dialysis session,
• bioimpedance analysis not used within recent 3 months
• dry weight regarded as adequate according to the patient's responsible doctor
• the ability to understand and willingness to sign an informed consent statement.

Exclusion Criteria:

• acute infection within 1 month
• active rheumatic disease, or current on cortical steroid medication or cytotoxic medication
• uncontrolled neoplasm
• acute myocardial infarction within 1 month
• congestive heart failure (NYHA 3 - 4)
• stroke within 3 months,
• metallic installation, like contraceptive device, artificial joint(s)
• amputation
• female of childbearing age who has a pregnancy plan, or is pregnant, or on breast feeding
• having a plan to reduce dialysis frequency
• having a renal transplantation plan or planning to transfer to peritoneal dialysis within 3 years
• participating or planning to participate another clinical trial, which will confound the current study