Who will be blinded
This will be an unmasked trial, only the statistician will be blinded.
Data collection and management
Plans for assessment and collection of outcomes
Prior to this trial, the infusion procedures must be optimized and standardized for all patients. Each research unit will refer to its own protocols for infection surveillance and prevention, although respecting some minimal standard criteria and indications, common and approved by all research units. In each Center the infusions lines must be the same for both intervention arms and differ only in the presence or absence of the filter.
Data will be collected daily from enrolment up to 48 h after discontinuation of infusion therapy.
Each catheter placed in the patients of the two arms will be recorded, and at the time of the removal the cause (obstruction, expiration date, etc.) will be specified.
In case of inflammatory events, patients will undergo to defined specimens, as always in correct clinical practice: complete blood count, sepsis biomarkers (C- reactive protein, procalcitonin, presepsin) and cultures (blood cultures and/or catheter tip culture; discretionary, lumbar culture and/or urine culture, based on clinical suspicious).
At discharge information regarding the main neonatal pathologies will be recorded.
Local principal investigators participated in preparatory meeting in which details on study protocol, how to optimize infusion lines, filtering strategies and data collection were accurately discussed. The full protocol will be available on the INCAS password-protected platform, to which research units will have access. To resolve difficulties, it will be possible to contact the INCAS Trial Coordinating Unit ([email protected])
Plans to promote participant retention and complete follow-up
All patients will be followed from recruiting to discharge from the NICU. No follow-up after discharge is planned.
Data management
All data to be collected will be obtained from the clinical records. Data will be recorded on a common database available on the INCAS website and specifically designed for this study. Access to the database will be password protected, and data will be recorded by trained operators for each centre. Participants will be identified by trial number only. The software provides input checks to reduce the possibility of input errors.
Confidentiality
Data security and anonymity is ensured by the use of access passwords and special encryption procedures.
Statistical methods
Statistical methods for primary and secondary outcomes
The trial will be analyzed and reported using the SPIRIT reporting guidelines.
The analysis will be performed on the "full analysis set" (FAS), i.e., all infants included in the study who did not violate the main requirements of the protocol. Infants whose parents withdrew informed consent, died or transferred to another center not participating in the study before a time of less than 48 hours after the interruption of the infusion therapy, with missing data on the primary outcome will be excluded from FAS. An additional analysis will be performed on the "per protocol set" (PPS) including only subjects who did not violate the protocol (infants who did not switch arms and discharged home). Reasons for exclusion from both FAS and PPS will be described in the analysis.
The primary outcome will be assessed using two-tailed Fisher's exact test (without covariates). Further analysis will be performed using generalized linear models in which the number of catheters/neonate and catheter maintenance time will be considered as adjustment variables. If the sample is unbalanced, gestational age and center will be included as covariates.
Secondary outcomes will be assessed similarly to the primary outcome if possible, or with other appropriate generalized linear models.
Interim analyses
An interim analysis is planned upon reaching the enrollment of half of the patients expected by the sample size calculation.
Plans to give access to the full protocol, participant level-data and statistical code
Data will be available with investigator support in deidentified participant data form at the time of the publication of the trial results. Investigators will be able to access data for future ancillary studies and meta-analyses after author approval (INCAS Trial Coordinating Unit).
Oversight and monitoring
Composition of the coordinating center and trial steering committee
The Coordinating Center is composed of a Center Director (Chair) who supervises and guarantees all activities; a Principal Investigator (PI) who coordinates the activities of all participating centers; some co-investigators involved in consent collection, randomization, data collection and database entry; an engineer who ensures the security and integrity of the database and a biostatistician who will perform the final analyses. A local PI will be identified in each center, coordinating enrollment and own center data collection.
Composition of the data monitoring committee, its role and reporting structure
The study protocol has been notified to the Clinical Trial Quality Team of the “Città della Salute e della Scienza di Torino”, who has the authority to stop the trial early if patient safety is compromised and to check procedures accuracy and data integrity.
Adverse event reporting and harms
This study does not involve the use of drugs or devices capable of causing adverse events. However, the data collection software contains a section for reporting comorbidities and any adverse events.
Frequency and plans for auditing trial conduct
INCAS Trial Coordinating Unit is available to help Centers every day. Every 3 months a report will be generated, containing the list of incomplete records, and Centers will be notified.
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees)
Any changes to the protocol will be presented to the centers on video call and the revisions will be available through the database platform.
Dissemination plans
The results will be published on international journals and presented at the main national and international congresses.