Frequent Hemodialysis Network: Nocturnal Trial

The Frequent Hemodialysis (FHN) Nocturnal Trial is a randomized controlled trial recruiting subjects from dialysis units associated with designated Clinical Centers in the U.S. and Canada and followed for 12 months. Subjects will be randomized to conventional hemodialysis delivered three days per week home arm or to the six times per week nocturnal home hemodialysis arm which will follow any dialysis prescription provided their prescribed standardized Kt/V is at least 4.0 and treatment time is at least 6.0 hours, six times per week.

This trial is a randomized, unblinded study of six times per week nocturnal home hemodialysis versus three times per week home hemodialysis. A target of 150 patients will be enrolled into this study with equal allocation in each arm, stratified by Clinical Center and residual renal function. All patients will be assessed for suitability for nocturnal home hemodialysis using a standardized method prior to patients entering the baseline portion of this protocol. The minimum dialysis dose in the standard arm will be an equilibrated Kt/V of 1.1 (equivalent to a standardized Kt/V (sKt/V) of 2.0) AND a minimum time of 2.5 hours. In the nocturnal arm there will be a minimum prescription of six hours per session for six days per week AND a minimum standardized Kt/V of 4.0. Patients will be followed for 12 months. Two co-primary outcomes are designated: 1) a composite of mortality with the change over 12 months in the SF-36 RAND physical health composite, and 2) the change over 12 months in left ventricular mass. In addition, first priority secondary outcomes have been designated for seven outcome domains: 1) cardiovascular structure and function (change in LV mass), 2) physical function (change in the PHC), 3) depression/burden of illness (change in Beck Depression Inventory), 4) nutrition (change in serum albumin), 5) cognitive function (change in the Trail Making Test B), 6) mineral metabolism (change in average predialysis serum phosphorus), and 7) clinical events (rate of non-access hospitalization or death). Hypertension and anemia are also main outcome domains, but without designation of single first priority outcomes. The cost-effectiveness of the two interventions will also be compared. The objectives of the study are as follows: Feasibility: To determine the feasibility of recruiting and retaining patients in a randomized trial of six times per week at-home nocturnal hemodialysis versus standard three times per week at home hemodialysis. To determine patient adherence and acceptance of nocturnal hemodialysis, and to identify reasons for discontinuation or noncompliance to the interventions. Safety: To determine the safety of the nocturnal hemodialysis intervention, with a particular emphasis on vascular access and patient burden. Efficacy: To evaluate the efficacy of six times per week nocturnal HD compared to conventional three times per week HD on two co-primary outcomes: i) a composite of mortality with the change over 14 months in left ventricular mass by magnetic resonance imaging, and ii) a composite of mortality with the change over 14 months in the SF-36 RAND physical health composite score (PHC). To determine the effect of six times per week nocturnal HD on nine secondary outcome domains: i) cardiovascular structure and function, ii) physical function, iii) depression/burden of illness, iv) nutrition, v) cognitive function, vi) mineral metabolism, vii) clinical events, viii) hypertension, and ix) anemia. Characterization of Interventions: To characterize the six times per week nocturnal home hemodialysis intervention in comparison to standard home three times per week hemodialysis, including evaluation of small and middle molecule solute clearance, treatment time, and volume removal. Implementation: To determine the feasibility of implementing six times per week nocturnal home hemodialysis in practice, including evaluation of barriers to implementation such as the home environment and any potential incremental costs of nocturnal home hemodialysis compared to three times per week conventional hemodialysis. An evaluation of the cost effectiveness of six times per week home nocturnal HD relative compared to 3 times per week conventional home HD will be performed.

a composite of 12 month mortality and the change over 12 months in the SF-36 RAND physical health composite

cardiovascular structure/funct (change in LV mass over 12 mos), health-related QoL/phys funct (change over 12 mos in PHC),

depression/dis burden (change over 12 mos in Beck Depression Inv.),nutrition (change over 12 mos in serum albumin, cognitive funct (change over 12 mos in TrailMaking Test B),mineral metabolism (change over 12 mos in aveg pre-dialysis serum phosphorus),

Inclusion Criteria: Patients with end stage renal disease requiring chronic renal replacement therapy Age ≥ 18 years, Achieved mean eKt/V of ≥ 1.1 during Baseline Exclusion Criteria: GFR greater than 10 ml/min/1.73 m2 as measured by the average of urea and creatinine clearances obtained from a urine collection of at least 24 hours Expectation that native kidneys will recover kidney function Current access is temporary non-tunneled catheter Unable to follow the nocturnal home hemodialysis training protocol for any reason, including inability to train the patient or the patient's caregiver Non-compliance with hemodialysis or peritoneal dialysis treatments in the past Medical conditions that would prevent the patient from performing the cardiac MRI procedure (e.g., inability to remain still for the procedure, a metallic object in the body, including cardiac pacemaker, inner ear (cochlear) implant, brain aneurysm clips, mechanical heart valves, recently placed artificial joints, and older vascular stents) Unable to verbally communicate in English or Spanish Current requirement for hemodialysis more than three times per week due to medical comorbidity (ultrafiltration session on fourth day per week not an exclusion criteria) Currently on daily or nocturnal HD, or less than 3 months since the patient discontinued daily or nocturnal HD Scheduled for living donor kidney transplant, change to peritoneal dialysis, or plans to relocate to an area outside of the referral area of one of the Clinical Centers within the next 12 months Expected geographic unavailability at the Clinical Center (for standard arm patients) or at home (for nocturnal arm patients) for > 2 consecutive weeks or > 5 weeks total during the next 12 months (excluding unavailability due to hospitalizations) Less than 3 months since the patient returned after acute rejection resulting in allograft failure Currently in acute care or chronic care hospital Life expectancy less than six months A medical history that might limit the individual's ability to take trial treatments for the 12 month duration of the study, including: currently receiving chemo or radiotherapy for a malignant neoplastic disease other than localized non-melanoma skin cancer, active systemic infection (including tuberculosis, disseminated fungal infection, active AIDS but not HIV), and cirrhosis with encephalopathy Current pregnancy or planning to become pregnant within the next fourteen months (patients require a higher dose of dialysis if pregnant). All female patients that have not gone through menopause will need to use an effective contraceptive method while enrolled in the study. Contraindication to heparin, including allergy or heparin induced thrombocytopenia Current use of investigational drugs or participation in an interventional clinical trial that contradicts or interferes with the therapies or measured outcomes in this trial Unable or unwilling to follow the study protocol for any reason (including mental incompetence) Unable or unwilling to provide informed consent or sign IRB-approved consent form

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