Safety of Reduced Infliximab Infusion Time

Safety, Efficacy, and Cost-effectiveness of a Reduced Infliximab Infusion Time Protocol

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05340764

Enrollment

Registered

2022-04-22

Start date

2020-08-01

Completion date

2023-05-04

Last updated

2024-08-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Inflammatory Bowel Diseases

Brief summary

Remicade is a common medicine used for the treatment of inflammatory bowel disease. This medication is given as an intravenous infusion over 2 hours. Studies have suggested it is safe to give the infusion at a faster rate. The investigators would like to see if the infusion can be given over 1 hour. The investigators expect that increasing the rate of infusion WILL NOT lead to an increase in infusion reactions and will be just as safe and effective as the standard 2 hours dose.

Detailed description

1.1 Infliximab use in IBD Inflammatory bowel disease (IBD) affects 349 per 100,000 adults in the United States and is associated with significant morbidity and mortality. Infliximab is an effective and commonly used medication to treat patients with IBD, but a main safety concern is an antibody-induced infusion reaction. The incidence of infusion reactions is \ 6.5%, with mild, moderate, or severe reactions occurring in 3.1%, 1.2%, and 1% of infusions, respectively. Because of the concern for infusions reactions, infliximab is FDA approved to be infused over 2 hours or more. The typical interval for infusions is every eight weeks but is at times reduced to every 4 weeks in patients with IBD. This infusion time represents a significant inconvenience to patients who receive regular maintenance infusions. 1.2 Accelerated Infliximab Infusions Multiple studies outside of the United States have demonstrated that a shortened infusion time to one hour, and even thirty minutes is safe and tolerable with similar rates of infusion reactions compared to an infusion time of two hours. However, these studies have differed in dosing, interval, pre-medication allowed in the study, and they are not randomized controlled studies. It has also been shown that reducing infusion times leads to cost savings and increased patient satisfaction. A recent study conducted in the United States at the University of California in San Francisco, confirmed that a shortened infusion time of one hour is safe and tolerated. 1.3 Rationale The hypothesis is that a shortened infusion time to one hour will be safe and tolerated, with equal infusion reaction rates compared to two-hour infusion

Interventions

DRUGInfliximab

Infliximab is an effective and commonly used medication to treat patients with IBD

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Must be at least 18 years of age 2. Must have a diagnosis of IBD 3. Must be receiving Infliximab or biosimilar drug infusions for IBD at one of the study infusion centers - Center for Advanced Medicine, Barnes-Jewish West County, Barnes-Jewish South County infusion centers, or receiving infusion through BJC Home Care Services/ Barnes Home Health Company. 4. Must tolerate the three induction doses or be tolerating current maintenance dosing without an infusion reaction to qualify for randomization.

Exclusion criteria

1. Those receiving Infliximab for an indication other than IBD (the investigators will include patients receiving infliximab or biosimilar drug for both IBD and an additional autoimmune disease) 2. Patients with history of a moderate or severe infusion reactions to infliximab or to an infliximab biosimilar as defined in section 7 3. Patients with known antidrug antibodies to infliximab 4. Patients who are restarting infliximab (patients who have received infliximab within the past year but have now had an interval greater than 13 weeks between prior dose) must tolerate the three induction doses to qualify for randomization 5. Patients receiving an additional infusion concomitant with infliximab (e.g. IV iron) 6. Patients who decline to participate in the trial

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Acute Infusion Reaction as Assessed by the Nursing Staff of the Infusion Unit	Median of 12 months in the control and a median of 14 months in the study group.	Acute infusion reaction is defined as any reaction occurring during or within 1 hour after completion of the infusion. It will be separated into mild reactions and moderate/severe reactions as outlined below. Mild/Localized Reaction Pruritus Flushing (facial erythema) Rash/Urticaria Rigors Swelling Moderate/Severe Reaction Fever (temperature \> 38.3 degree Celsius) Heart Rate greater than 120 Dyspnea/Shortness of breath Decrease in consciousness Hypotension defined as decrease in baseline SBP by \>20 mmHg or SBP \<85 Bronchospasm or laryngospasm Anaphylactic shock of one hour, to the standard two-hour infusion.

Secondary

Measure	Time frame	Description
Cost Saving Analysis	Median of 12 months in the control and a median of 14 months in the study group.	Direct costs of the 2 hour infusion per-infusion per-patient in dollar amount will be compared to direct costs of the 1 hour infusion per-infusion per-patient in dollar amount in our institution and the difference will be reported. Nursing Cost and Chair Occupancy Cost obtained from BJH Human Resources Department.
Effect of Concomitant Immunomodulators and Pre-medications on Rate of Infusion Reactions - Median Number of Infusions	Median of 12 months in the control and a median of 14 months in the study group.	Assess effect of concomitant immunomodulators and pre-medications on rate of infusion reactions - Median number of infusions
Number of Infusions Where Concomitant Immunomodulators and Pre-medications Were Used	Median of 12 months in the control and a median of 14 months in the study group.	Number of Infusions where Concomitant Immunomodulators and Pre-medications were used in the study
Effect of Concomitant Immunomodulators and Pre-medications on Rate of Infusion Reactions - Duration of Follow up (in Months)	Median of 12 months in the control and a median of 14 months in the study group.	Assess effect of concomitant immunomodulators and pre-medications on rate of infusion reactions - Duration of follow up (in months)

Countries

United States

Participant flow

Recruitment details

Participants were recruited from 2020 to 2021 and followed throughout the study after enrollment. Patients aged 18 years or older with an established diagnosis of IBD, receiving infliximab at one of our infusions centers and have tolerated the 3 induction doses and current maintenance dosing were eligible for inclusion in the study.

Pre-assignment details

Patients were excluded if they were receiving infliximab exclusively for a non-IBD indication, had a history of moderate or severe infusion reactions to infliximab (or biosimilar), had known antidrug antibodies to infliximab, had an interval greater than 13 weeks from prior dose of infliximab, were receiving an additional infusion concomitant with infliximab (eg, IV iron), or declined to participate in the trial.

Participants by arm

Arm	Count
2-hour Infusion of Infliximab 2 hour infusion of infliximab Infliximab: Infliximab is an effective and commonly used medication to treat patients with IBD. Patients in this group received the standard 2 hour infusion of infliximab and serves as the control group.	45
1-hour Infusion of Infliximab 1 hour infusion of infliximab Infliximab: Infliximab is an effective and commonly used medication to treat patients with IBD	51
Total	96

Baseline characteristics

Characteristic	2-hour Infusion of Infliximab	1-hour Infusion of Infliximab	Total
Age, Continuous	47 years STANDARD_DEVIATION 15.5	47 years STANDARD_DEVIATION 15.5	47 years STANDARD_DEVIATION 15.5
Concomitant Immunomodulator 6-MP	8 Participants	5 Participants	13 Participants
Concomitant Immunomodulator AZA	9 Participants	11 Participants	20 Participants
Concomitant Immunomodulator MTX	5 Participants	10 Participants	15 Participants
Concomitant Immunomodulator None	23 Participants	25 Participants	48 Participants
Inflammatory Bowel Disease Type Crohn's Disease patients	34 Participants	41 Participants	75 Participants
Inflammatory Bowel Disease Type Ulcerative Colitis patients	11 Participants	10 Participants	21 Participants
Race and Ethnicity Not Collected	—	—	0 Participants
Region of Enrollment United States	45 participants	51 participants	96 participants
Sex: Female, Male Female	22 Participants	23 Participants	45 Participants
Sex: Female, Male Male	23 Participants	28 Participants	51 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 45	0 / 51
other Total, other adverse events	0 / 45	0 / 51
serious Total, serious adverse events	0 / 45	0 / 51

Outcome results

Primary

Number of Participants With Acute Infusion Reaction as Assessed by the Nursing Staff of the Infusion Unit

Acute infusion reaction is defined as any reaction occurring during or within 1 hour after completion of the infusion. It will be separated into mild reactions and moderate/severe reactions as outlined below. Mild/Localized Reaction Pruritus Flushing (facial erythema) Rash/Urticaria Rigors Swelling Moderate/Severe Reaction Fever (temperature \> 38.3 degree Celsius) Heart Rate greater than 120 Dyspnea/Shortness of breath Decrease in consciousness Hypotension defined as decrease in baseline SBP by \>20 mmHg or SBP \<85 Bronchospasm or laryngospasm Anaphylactic shock of one hour, to the standard two-hour infusion.