A Clinical Trial of IntensiVE Dialysis (ACTIVE)

• Survival and cardiovascular analyses [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
• Quality of life and patient acceptability [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Safety outcomes [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
• Costs associated with each intervention [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Changes in biochemical and haematological parameters [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

• Safety of extended hours haemodialysis [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
• Durability of extended hours haemodialysis [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Change in systolic blood pressure taken as the average of 3 recumbent measurements taken after 5 minutes rest and measured on the day after a dialysis session [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Pre-dialysis serum phosphate levels, calcium phosphate product levels, and dose of phosphate binders at 4 and 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Predialysis haemoglobin concentration and dose of erythropoietic agents at 4 and 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Time to the occurrence of a combined end-point consisting of new onset of acute myocardial infarction, stroke or death due to cardiovascular causes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Time to access failure, defined as thrombosis or stenosis of the fistula requiring revision [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• time to first access related infection [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Persistence of therapy at 24 months, 36 and 60 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Vital status at 24, 36 and 60 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• proportion of the individuals who are invited to participate in the study that then proceed to randomisation and receive at least one session of randomised therapy [ Time Frame: 2 months from randomisation ] [ Designated as safety issue: No ]
• hospital admissions (days per year) excluding any admissions solely for routine dialysis [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• hospital admissions (events per year) excluding any admissions solely for routine dialysis [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• A formal cost-utility analysis will be conducted from the perspective of the health care provider to estimate cost per quality adjusted life year gained. Evaluations will be conducted for the whole patient group and for home and centre-based therapies. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• non-hospital health service use such as GP consultations and non-hospital medications [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• employment status [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• household financial stress as measured by whether individuals' report an inability, or the need for assistance, in making household payments in the previous 3 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• requirement for blood pressure lowering drugs [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• change in left ventricular mass from baseline to 12 months measured by magnetic resonance imaging [ Time Frame: 12 months ] [ Designated as safety issue: No ]

A rapidly increasing volume of observational data suggests substantial benefits may be associated with an increased duration of dialysis. As well as improved quality of life, improved functioning and beneficial changes in a variety of laboratory parameters, it has been suggested that extended dialysis sessions might reduce mortality and major morbidity. Uncontrolled data from centres that have been providing extended dialysis shows dramatically lower mortality rates compared to those observed in centres providing standard duration dialysis. Recent analyses of extended dialysis conclude that the savings achieved in drug and hospitalization costs may lead to an overall reduction in costs compared with traditional forms of dialysis.

In this trial, we propose to examine the effects of extended dialysis (24 hours weekly or more) compared to standard dialysis (18 hours or less weekly) in patients with ESKD. The proposed study is a multi-centre, open label, randomised, controlled trial.

The study began with a pilot phase which was converted to the current main study on the receipt of peer-reviewed funding for the full study.

• Renal Replacement Therapy
• Renal Dialysis
• End Stage Kidney Disease
• End Stage Renal Disease
• Uremia

• Experimental: extended hours
  24 or more hours per week of hemodialysis
  Intervention: Procedure: haemodialysis
• Active Comparator: standard hours
  18 or less hours per week of hemodialysis
  Intervention: Procedure: haemodialysis

• Jardine MJ, Zuo LI, Gray NA, de Zoysa J, Chan CT, Gallagher MP, Howard K, Hertier S, Cass A, Perkovic V; ACTIVE Dialysis Steering Committee. Design and participant baseline characteristics of 'A Clinical Trial of IntensiVE Dialysis': the ACTIVE Dialysis Study. Nephrology (Carlton). 2015 Apr;20(4):257-65. doi: 10.1111/nep.12385.
• Eriguchi R, Taniguchi M, Ninomiya T, Hirakata H, Fujimi S, Tsuruya K, Kitazono T. Hyporesponsiveness to erythropoiesis-stimulating agent as a prognostic factor in Japanese hemodialysis patients: the Q-Cohort study. J Nephrol. 2015 Apr;28(2):217-25. doi: 10.1007/s40620-014-0121-9. Epub 2014 Jul 31.
• Badve SV, Hawley CM, Johnson DW. Frequent versus standard hemodialysis. N Engl J Med. 2011 Mar 10;364(10):975; author reply 976. doi: 10.1056/NEJMc1100105#SA3.

Inclusion Criteria:

1. Incident or prevalent patients requiring maintenance haemodialysis therapy for ESKD
2. Aged 18 years or older
3. Undergoing dialysis for 18 hours per week or less
4. Suitable for either extended or standard dialysis in the view of the treating physician
5. Agreeable to randomisation

Exclusion Criteria:

1. Life expectancy of less than 6 months
2. Definite plans to undergo renal transplantation within 12 months of entry to the study
3. Inability to complete quality of life questionnaire
4. Concomitant major illness that would limit assessments and followup
5. High chance that the patient will not adhere to study treatment and follow up in the view of the treating physician.

• National Health and Medical Research Council, Australia
• Baxter Healthcare Corporation