Our primary objective in this study is to compare the incidence of infusion reactions of
Infliximab when administered over 30 minutes versus 60 minutes. We hypothesize that there
will be no significant differences between the two groups, demonstrating that 30-minute
infusions are as safe and effective as the current standard of 60-minute infusions.
Secondary endpoints include evaluating patient and nurse satisfaction with both infusion
rates, as well as assessing resource utilization by measuring total outpatient clinic
stay and nursing staff allocation.
Additionally, we will explore whether satisfaction, infusion reactions and treatment
effectiveness (asessed through clinical scoring systems, endoscopic findings and
laboratory results) are affected by patient demographics (such as age, sex), disease
type, infusion frequency, or co-treatment with immunomodulators.
Project methodology Study design and implementation Strategy The iRAPID study is designed
as a prospective, randomized, open-label, non-inferiority crossover trial designed to
compare the safety and effectiveness of 30-minute versus 60-minute infliximab infusions
in pediatric IBD patients. The study will be conducted at the Akershus University
Hospital Pediatric and Adolescent Outpatient Clinic, where all included patients already
receive infliximab infusions for inflammatory bowel disease (IBD). Patients included in
the study will be randomized to receiving four consecutive fast 30-minute infusions, or
four consecutive standard 60-minute infusions, after which they will switch to the
alternative regimen. Each patient will serve as their own control. Randomization will be
performed using a validated computer-generated randomization program.
If the patient meets inclusion and exclusion criteria, they will be invited to
participate in the study. Written consent will be obtained from parents for children
under the age of 16, while patients aged 16 years or older will provide their own written
consent. Participation is voluntary, and one may withdraw from the study and return to
the standard infusion rate of 60 minutes at any time. Based on the power calculation, 60
patients will be included in the study. This sample size allows for adjustments in
dosing, intervals, and concomitant medication according to standard clinical criteria, as
well as a safety margin for dropouts.
Infusion reactions will be monitored by an experienced IBD-nurse before, during and after
each infusion. Infusion reactions will be dichotomized as yes or no, and categorized as
mild/localized, moderate or severe using predefined clinical criteria (See references
Lichtenstein, J Crohns Colitis. 2015;9(9):806-15 and Jagt et al, J Pediatr Gastroenterol
Nutr. 2023;77(3):373-80). The criteria are based on age-appropriate values from the
Pediatric Early Warning Score (PEVS), which ensures consistency in event classification
and facilitates reliable safety assessments. The nurse will record vital signs, including
pulse, blood pressure and respiratory rate, in addition to observe for symptoms of an
infusion reaction, in accordance with the already established standard procedure for
infliximab infusions.
Criteria for mild/localized infusion reaction: Transient and short-lived pruritus,
flushing (facial erythema), myalgia or low-grade fever (37.5-37.9°C).
Criteria for moderate infusion reaction: Fever (temperature >38°C), tachycardia
(increase in heart rate >20 beats/min above age-appropriate values in the PEVS
chart), sensation of breathlessness or chest tightness or angioedema.
Criteria for severe infusion reaction: Bronchospasm or laryngospasm, decreased
consciousness, hypotension (a drop in systolic blood pressure >20 mmHg from the
normal value in the PEVS chart) or anaphylactic shock.
If an infusion reaction occurs, the patient will be assessed with a doctor, and
appropriate intervention will follow standard clinical guidelines (Ref Lichtenstein, J
Crohns Colitis. 2015;9(9):806-15). In case of an infusion reaction, clinical judgment
will be used to assess whether there is an identifiable cause, whether the patient should
continue the medication, whether additional treatment is necessary, and how the next
infusion should be conducted. All adverse events, including symptoms, interventions, and
assessments will be documented in the medical record and the study database.
In the case of a mild infusion reaction, the infusion rate will be reduced and then
gradually increased if tolerated.
In the case of a moderate infusion reaction, the infusion will be stopped,
pharmacological interventions will be considered and if the patient is deemed
stable, the infusion will restart at a slower rate with gradual escalation.
In the case of a severe infusion reaction, the infusion will be stopped immediately,
and appropriate treatment will be administered.
Demographic data are recorded to describe the enrolled patients, including age, sex,
weight and height, and disease-specific information such as IBD type, duration and
extent, and previous treatment including other immunosuppressive treatment, treatment
efficacy, and the duration and number of doses of infliximab therapy prior to study
inclusion. At each infusion visit, the doctor will also document infliximab dose,
infusion interval, and drug concentration. As part of the routine consultation, disease
activity will be assessed using validated scoring systems: PUCAI for ulcerative colitis
and short-PCDAI for Crohn's disease. Adjustments to treatment intervals and dosing will
be made based on clinical jugdements and patient needs, independent of study
participation.
Satisfaction will be evaluated using a custom-designed questionnaire completed by
patients, parents and nurses. This assessment will provide qualitative insights into the
impact of infusion time on both patient/caregiver experience and the clinical workflow.
The economic impact of infusion-rate will be assessed by recording:
Total time spent in the outpatient clinic from arrival to discharge
Total nursing time required for each infusion, including preparatory tasks (blood
sampling, IV placement), infusion administration, monitoring of the patient and
documentation.