Evaluation of efficacy, outcomes and safety of infant haemodialysis and ultrafiltration in clinical use: I-KID a stepped wedge cluster RCT
Authors: Lambert Heather , Hiu Shaun , Coulthard Malcolm , Matthews John N S , Wood Ruth , Crosier Jean , Agbeko Rachel , Brick Thomas , Duncan Heather , Grant David , Mok Quen , Nyman Andrew Gustaf , Pappachan John , Wellman Paul , Boucher Chris , Bulmer Joe , Chisholm Denise , Cromie Kirsten , Emmet Victoria , Feltbower Richard , Grayling Michael , Harrison Rebecca , Holstein Eva-Maria , Kennedy Ciara A , McColl Elaine , Morris Kevin , Norman Lee , Office Julie , Parslow Roger , Pattinson Christine , Sharma Shriya , Smith Jonathan , Steel Alison , Steel Rachel , Straker Jayne , Vrana Lamprini , Walker Jenn , Whitaker Mike , Wightman Jim , Wilson Nina , Wirz Lucy 
Published: January 2024

Abstract
Background
Critically unwell babies in intensive care units may develop acute renal failure. Options for renal replacement therapy are limited by their small size and available technology.

Objectives
To determine the clinical efficacy, outcomes and safety profile of the NIDUS® (a novel infant haemodialysis device) for babies under 8 kg, compared with current renal replacement therapy.

Design
A clinical investigation using a non-blinded cluster stepped wedge design with paediatric intensive care units randomised to sequences.

Setting
Paediatric intensive care units in six UK hospitals.

Participants
Children under 8 kg who required renal replacement therapy for fluid overload or biochemical disturbance.

Interventions
Continuous renal replacement therapy was provided by the usual methods: peritoneal dialysis and continuous haemofiltration (during control periods) and by the NIDUS (during intervention periods), a novel device designed for babies with a smaller circuit and filter and volumetric control of ultrafiltration.

Main outcome measures
Primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances, accuracy of reported ultrafiltration and mortality.

Data sources
Bedside study data collected by weighing bags of fluid entering and leaving the device were entered into the study database along with case descriptors. Some secondary outcome data was collected via the Paediatric Intensive Care Audit Network.

Results
Ninety-seven participants were recruited by study closure, 62 to control and 35 to intervention. The primary outcome was obtained from 62 control but only 21 intervention patients, largely because of technical difficulties using NIDUS. The analysis comparing the available primary outcomes showed that ultrafiltration with NIDUS was closer to that prescribed than with control: standard deviations controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018.
The mean clearances for creatinine, urea and phosphate were lower on peritoneal dialysis than NIDUS, which were in turn lower than continuous veno-venous haemofiltration. The variability in the clearances was in the same order.
Of the 62 control patients, 10 died (2/62 on peritoneal dialysis; 7/13 on continuous haemofiltration) before discharge from paediatric intensive care unit (16%), compared with 12 out of 35 (34%) in the NIDUS group: p = 0.04, 95% confidence interval for difference (0 to 36%).

Harms
No important adverse events occurred and the NIDUS has an acceptable safety profile compared with other renal replacement therapies in this critically ill population with multi-organ failure. Mortality was lowest for Peritoneal Dialysis, highest for continuous haemofiltration, with the NIDUS in-between. Only one serious adverse device event which was reported to the Medicines and Healthcare products Regulatory Agency.

Conclusions
NIDUS works effectively, delivering appropriate blood clearances and accurate, controllable fluid removal (ultrafiltration), indicating that it has an important place alongside other dialysis modalities for infant renal replacement therapy.

Future work
Findings from this study indicate some modifications are required to NIDUS to improve usability. Further studies on use of the NIDUS device in other populations of babies for example those with chronic renal failure, and long-term outcomes are required.

Trial registration
This trial is registered as ISRCTN 13787486.

Funding
This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/23/26) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 1. See the NIHR Funding and Awards website for further award information.