Preventing adverse events during paediatric cancer treatment: protocol for a multi-site hybrid randomised controlled trial of catheter lock solutions (the CLOCK trial).

INTRODUCTION: Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock. METHODS AND ANALYSIS: This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers. ETHICS AND DISSEMINATION: Ethics approval has been provided by Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000499785.

Pediatric invasive device utility and harm: a multi-site point prevalence survey.

BACKGROUND AND AIMS: Invasive devices are widely used in healthcare settings; however, pediatric patients are especially vulnerable to invasive device-associated harm. This study aimed to explore invasive device utility, prevalence, harm, and clinical practice across three Australian pediatric tertiary hospitals. METHODS: In 2022-2023, a multi-center, observational, rolling-point-prevalence survey was conducted. Fifty-per-cent of inpatients were systemically sampled by random allocation. Patients with devices were then followed for up to 3-days for device-related complications/failures and management/removal characteristics. RESULTS: Of the 285 patients audited, 78.2% had an invasive device (n = 412 devices), with a median of 1 device-per-patient (interquartile range 1-2), with a maximum of 13 devices-per-patient. Over half of devices were vascular access devices (n = 223; 54.1%), followed by gastrointestinal devices (n = 112; 27.2%). The point-prevalence of all device complications on Day 0 was 10.7% (44/412 devices) and period-prevalence throughout the audit period was 27.7% (114/412 devices). The period-prevalence of device failure was 13.4% (55/412 devices). CONCLUSIONS: The study highlighted a high prevalence of invasive devices among hospitalized patients. One-in-ten devices failed during the audit period. These findings underscore the need for vigilant monitoring and improved strategies to minimize complications and enhance the safety of invasive devices in pediatric hospital settings. IMPACT: A high prevalence of invasive devices among hospitalized patients was reported. Of the 285 patients audited, almost 80% had an invasive device (total 412 devices), with a median of 1 device-per-patient and a maximum of 13 devices-per-patient. The most common devices used in pediatric healthcare are vascular access devices (n = 223; 54.1%), however, 16% (n = 36) of these devices failed, and one-third had complications. The point prevalence of all device complications at day 0 was 10.7% (44 out of 412 devices), with a period prevalence of 27.7% (114 out of 412 devices) throughout the audit period.

Invasive device-associated skin complications and mechanical dysfunctions in paediatric healthcare: A systematic review and meta-analysis.

AIM: This study aimed to estimate the proportion and rate of skin complications and mechanical dysfunction associated with indwelling invasive devices in paediatric healthcare. DESIGN: This systematic review is reported in accordance with Cochrane standards for randomized controlled trials and the Meta-analysis of Observation Studies in Epidemiology for cohort studies. DATA SOURCES: MEDLINE, CINAHL, Embase, Web of Science, Scopus, Cochrane CENTRAL, clinical trial registries, and unpublished study databases were searched. REVIEW METHODS: Cohort studies and trials published from January 2011 to June 2022, including (1) indwelling invasive devices, (2) paediatric participants admitted to a hospital, (3) reporting post-insertion device-associated skin complication and/or mechanical dysfunction, and (4) published in English, were included. Device-associated skin complication and mechanical dysfunction (infiltration, leakage, occlusion/blockage, dislodgement/malposition, breakage and others). Pooled proportion and incidence rate per 1000 device days are reported. RESULTS: This review synthesized 114 studies (30,782 devices; 1,635,649 device-days). Skin complications were reported in 40 studies, but none exclusively reported individual device-related pressure injuries. Mechanical dysfunctions were well-reported for central venous access devices, peripheral intravenous catheters, nasogastric/gastric tubes and peritoneal dialysis catheters but less for arterial catheters, extracorporeal membrane oxygenation and ventricular assist devices. CONCLUSIONS: This systematic review highlights the need for standardized definitions and reporting methods to better surveil and benchmark device-related complications, particularly for understudied device types. Device-related pressure injuries were not reported in any of the included studies, and all devices except for vascular access devices require standardized reporting of complications. IMPACT: Despite the widespread use of invasive devices, comprehensive data on their prevalence, utility, and associated paediatric complications is limited. This review identified prevalent skin complications, occlusions and dislodgments in children with devices, underscoring the need for standardized reporting to enhance surveillance and understanding of paediatric device-related complications. REPORTING METHOD: MOOSE (Meta-analyses Of Observational Studies in Epidemiology) Checklist. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) affect about 25% of children with cancer, and treatment failure is common. Adjunctive ethanol lock therapy might prevent treatment failure but high-quality evidence is scarce. We evaluated ethanol lock therapy as treatment and secondary prophylaxis for CLABSI in children with cancer or haematological disorders. METHODS: This randomised, double-blind, placebo-controlled superiority trial, with two interim futility and efficacy analyses (done when the first 46 and 92 evaluable participants completed study requirements), was done at two paediatric hospitals in the USA and Australia. Patients aged 6 months to 24 years, inclusive, with cancer or a haematological disorder and new CLABSI were eligible. Participants were randomly assigned (1:1) to receive either ethanol lock therapy (70% ethanol) or placebo (heparinised saline) for 2-4 h per lumen daily for 5 days (treatment phase), then for up to 3 non-consecutive days per week for 24 weeks (prophylaxis phase). The primary composite outcome was treatment failure, consisting of attributable catheter removal or death, new or persistent (>72 h) infection, or additional lock therapy during the treatment phase, and recurrent CLABSI during the prophylaxis phase. This trial is registered with ClinicalTrials.gov, number NCT01472965. FINDINGS: 94 evaluable participants were enrolled between Dec 14, 2011, and Sept 12, 2016, of whom 48 received ethanol lock therapy and 46 received placebo. The study met futility criteria at the second interim analysis. Treatment failure was similar with ethanol lock therapy (21 [44%] of 48) and placebo (20 [43%] of 46; relative risk [RR] 1·0, 95% CI 0·6-1·6; p=0·98). Some adverse events, including infusion reactions and catheter occlusion, were more frequent in the ethanol lock therapy group than in the placebo group. Catheter occlusion requiring thrombolytic therapy was more common with ethanol lock therapy (28 [58%] of 48) than with placebo (15 [33%] of 46; RR 1·8, 95% CI 1·1-2·9; p=0·012). Discontinuation of lock therapy because of adverse effects or patient request occurred in a similar proportion of participants in the ethanol lock therapy (nine [19%] of 48) and placebo groups (ten [22%] of 46; p=0·72). INTERPRETATION: Ethanol lock therapy did not prevent CLABSI treatment failure and it increased catheter occlusion. Routine ethanol lock therapy for treatment or secondary prophylaxis is not recommended in this population. FUNDING: American Lebanese Syrian Associated Charities to St Jude Children's Research Hospital and an Australian Government Research Training Scholarship.