Safety, Efficacy, and Cost-effectiveness of a Reduced Infliximab Infusion Time Protocol
Phase: PHASE4
Conditions: Inflammatory Bowel Diseases
Sponsor: Washington University School of Medicine

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Safety, efficacy, and cost-effectiveness of a reduced Infliximab infusion protocol 
 
 
Principal Investigator:  
Chien-Huan Chen, M.D., PhD. 
Division of Gastroenterology 
Washington University in St Louis School of Medicine 
660 South Euclid Ave 
St Louis MO 63110 
 
Coordinating Center: 
Washington University School of Medicine 
 
Co-Investigators:    
Suha Abushamma, M.D. 
 
 
Study Coordinator: 
Suha Abushamma, M.D. 
Statistician:  
 
To be determined 
 
 
 
Protocol Version: 1 
Amendment: 3 
Protocol Date: May 5, 2022 
 
 
 
 
 
 

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Safety, efficacy, and cost-effectiveness of a reduced Infliximab infusion protocol 
 
 
Principal Investigator Signature Page 
 
Principal Investigator (printed):
      
Name of Institution:
      
 
PI Signature 
 
 
 
 
 
Date 
By my signature, I agree to personally supervise the conduct of this 
study and to ensure its conduct in compliance with the protocol, 
informed consent, IRB/HRPO procedures, the Declaration of 
Helsinki, ICH Good Clinical Practices guidelines, and the 
applicable parts of the United States Code of Federal Regulations 
or local regulations governing the conduct of clinical studies. 
 
 
 
 

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TABLE OF CONTENTS 
 
1 
Background and Rationale ................................................................................ 4 
1.1 
Infliximab use in IBD ..................................................................................................... 4 
1.2 
Accelerated Infliximab Infusions .................................................................................... 4 
1.3 
Rationale ......................................................................................................................... 4 
2 
Objectives ........................................................................................................... 4 
2.1 
Primary Objective ........................................................................................................... 4 
2.2 
Secondary Objectives ..................................................................................................... 4 
3 
Eligibility Criteria ................................................................................................ 5  
3.1 
Inclusion Criteria ........................................................................................................... 5 
3.2 
Exclusion Criteria ........................................................................................................... 5 
3.3 
Inclusion of Women and Minorities ............................................................................ 5 
4 
REGISTRATION PROCEDURES ........................................................................ 5 
4.1 
Confirmation of Patient Eligibility ................................................................................. 5 
4.2 
Assignment of UPN ........................................................................................................ 5 
4.3 
Randomization ............................................................... Error! Bookmark not defined. 
5 
Study Procedures ............................................................................................... 6 
5.1 
Recruitment .................................................................................................................... 6 
5.2 
Intervention .................................................................................................................... 6 
6 
REGULATORY AND REPORTING REQUIREMENTS ........................................ 6 
7 
Data and Safety Monitoring Plan ....................................................................... 7 
8 
Statistical Considerations ................................................................................. 8 
8.1 
Sample Size Calculations ................................................................................................ 8 
8.2 
Analysis methods ............................................................................................................ 8 
 
References .......................................................................................................... 8 
 
 

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1 
Background and Rationale 
 
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 [1-2]. Infliximab is an effective and commonly 
used medication to treat patients with IBD, but a main safety concern is an antibody-induced 
infusion reaction [3]. 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 [4]. 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 [3].  
 
 
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 [5-13]. 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 [14]. 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 [15].  
 
 
1.3 
Rationale 
 
Our 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.   
 
 
2 
Objectives  
 
2.1 
Primary Objective 
 
To compare the safety and tolerability (infusion reaction rate) of an infliximab infusion time of 
one hour versus the standard two-hour infusion.   
 
2.2 
Secondary Objectives 
 
1. Cost savings analysis of shortened infliximab infusion time 
2. Assess effect of concomitant immunomodulators and premedications on rate of infusion 
reactions 
 
 
 

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3 
Eligibility Criteria 
 
3.1 
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 our infusion centers 
– Center for Advanced Medicine, Barnes-Jewish West County, or Barnes-Jewish South County 
infusion centers, or BJC home pharmacy 
4. Must tolerate the three induction doses or be tolerating current maintenance dosing without an 
infusion reaction to qualify for randomization. 
 
3.2 
Exclusion Criteria 
 
1. Those receiving Infliximab for an indication other than IBD (we 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 
 
 
3.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this trial. 
 
 
 
 
4 
REGISTRATION PROCEDURES 
 
 
4.1 
Confirmation of Patient Eligibility 
 
Confirm patient eligibility by collecting the information listed below through review of the electronic 
medical record (EMR). 
 
1. Patient name and contact information (telephone number, fax number and email address) 
2. Patient’s age, race, sex, and DOB 
3. Diagnosis of IBD 
4. Infliximab infusion history 
5. Assessment for exclusion criteria listed in 3.2 
 
 
4.2 
Assignment of UPN 
 
Each patient will be identified with a unique patient number (UPN) for this study.  Patients will also 
be identified by first, middle, and last initials.  If the patient has no middle initial, a dash will be used. 
 

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4.3 
Patient assignment  
 
Consenting and eligible participants will be randomly assigned to one of two arms using a research 
randomization tool. There will be one control arm and one intervention arm. Participants in the first 
arm will undergo a traditional infusion time of two hours. The second arm will be patients who 
undergo an infusion time of one hour. Infusion reaction will be recorded. Patients from the 
intervention groups who have a moderate or severe infusion reaction, as defined in section 7, will 
be removed from the intervention groups back to 2-h infusions. Their subsequent infusions will not 
be included in the final analysis of 2-h infusions.   
 
 
5 
Study Procedures 
 
5.1 
Recruitment 
 
Adult patients with IBD who are receiving or are scheduled to start infliximab infusions will be 
screened for inclusion in the study. Patients will be identified from the gastroenterology clinic as 
well as outpatient infusion centers in the Center for Advanced Medicine, Barnes-Jewish West 
County, or Barnes-Jewish South County locations. Those subjects who qualify for the study 
based on inclusion/ exclusion criteria will be invited to participate. Once eligibility is confirmed, the 
patient will be contacted by phone, or in person in the clinic or infusion center, by one of the 
members of the research team. They will discuss the purpose of the study, the three arms, risks, 
and benefits of the study using an approved phone script. The patient will then be invited to 
participate. The consent process will take place over the phone when the patient is contacted or 
in person when they present for an infusion. Those patients who wish to participate will provide 
verbal consent. They will then proceed with the scheduled infusions. Patient allocation will take 
place after the patient is consented and before the day of the infusion. 
 
5.2 
Intervention 
 
After consent is obtained the patients will be assessed for appropriateness of a shortened 
infusion time. Patient that have tolerated their three induction doses without an infusion reaction, 
as well as patients who are already on maintenance dosing and do not have a history of an 
infusion reaction, will be randomized to either receive a one hour infusion of infliximab, or to stay 
on the standard 2-h infusion. Infusion reactions will be recorded for each group as outlined in 
section 7. Additional information including IBD type, demographic information, pre-medication 
use, and concomitant immunomodulator therapy will be recorded as well. All infusion doses as 
well as infusion intervals will be eligible for inclusion in the study. Drug dosing and intervals will be 
determined by the prescribing physician and left to their discretion.   
 
Patients in the intervention group who develop a moderate or severe infusion reaction as defined 
in section 7 will be removed from the intervention group and placed back on 2-h infusions. These 
future infusions will not be included in the study. Patients with a mild infusion reaction will 
continue in their assigned group (intervention or control). 
 
 
6 
REGULATORY AND REPORTING REQUIREMENTS 
 
Rates of infusion reactions will be continuously recorded and reported to an oversight committee to allow 
for safety monitoring.  
 
 
 

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7 
Data and Safety Monitoring Plan 
 
Acute infusion reactions will be defined as any reaction occurring during or within 1 hour after completion 
of the infusion. They will be separated into mild reactions and moderate/severe reactions as outlined 
below.  
1. Mild/Localized Reaction 
a. Pruritus  
b. Flushing (facial erythema) 
c. Rash/Urticaria 
d. Rigors 
e. Swelling 
2. Moderate/Severe Reaction 
a. Fever (temperature > 38.3 degree Celsius) 
b. Heart Rate greater than 120 
c. Dyspnea/Shortness of breath 
d. Decrease in consciousness 
e. Hypotension defined as decrease in baseline SBP by >20 mmHg or SBP <85 
f. 
Bronchospasm or laryngospasm 
g. Anaphylactic shock 
The treatment plan for infusion reactions will be as follows: 
1. Mild/Localized Reaction 
a. Pruritus, flushing, rash, or swelling 
i. Stop infusion 
ii. Administer diphenhydramine 25mg IV x 1 
iii. Administer famotidine 20mg IV x 1 
iv. Repeat steps ii, and iii x 1 PRN if no symptom improvement after 15 min. 
v. Notify MD 
vi. Vital signs every 15 minutes until symptoms resolve 
vii. After symptom resolution, restart infusion at 50% of previous rate 
b. Rigors 
i. Stop infusion 
ii. Administer meperidine 25mg IV x 1 only (not to be given if greater than 2 hours 
post infusion cessation) 
iii. Notify MD 
iv. Vital signs every 15 minutes until symptoms resolve 
v. After symptom resolution, restart the infusion at 50% of previous rate 
2. Moderate to Severe Reactions 
a. Stop infusion 
b. Administer diphenhydramine 50mg IV x 1 
c. Administer methylprednisolone 125mg IV x 1 
d. Administer famotidine 20mg IV x 1 
e. Repeat steps b, c, and d x 1 PRN if symptoms do not resolve within 15 min. 
f. 
If hypotension occurs (decrease in baseline SBP by >20 mmHg or SBP <85mmHg 
i. Administer epinephrine (1:1000) 0.3mg IM x 1. Repeat x 1 PRN if hypotension 
does not resolve within 15 min. 
g. Administer normal saline IV, wide open 
h. Place nasal cannula oxygen at 2L/minute 
i. 
Notify MD 

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j. 
Check vital signs every 5 minutes until stable, then every 15 minutes until symptoms 
resolve 
k. The time and rate of infusion restart to be determined by MD 
 
 
8 
Statistical Considerations  
 
8.1 
Sample Size Calculations 
 
Our sample size calculation was based on an infusion reaction rate of 3%, as suggested by 
recent studies. In order to show a non-inferiority of the accelerated infusion time assuming an 
infusion reaction rate of 3% while allowing for a 12% non-inferiority limit, a total of 90 patients (45 
in each group) would be needed. This would provide a power of 80% and significant alpha of 
0.05. 
   
8.2 
Analysis methods 
 
This study will collect both categorical and quantitative demographic variables, infusion details, and 
infusion reaction details. Premedication details and comcomitant immonomodulator therapy will 
also be recorded. All information will be transferred into an encrypted database. The categorical 
variables will be summarized using frequencies and percents, while the quantitative variables will 
be summarized using means and standard deviations. Chi square test will be used for categorical 
variables while student’s t test will be used for quantitative variables to test the difference between 
the study groups. Additionally, multivariable analysis will be used in order to identify factors 
associated with an increased risk of infusion reaction. The statistical software program SPSS will 
be used for analysis. A two-sided p value of < 0.05 will be considered significant. 
 
 
9 
References  
 
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