Clinical trial NCT03065244
Conditions: Mucocutaneous Lymph Node Syndrome
Keywords: Kawasaki disease
Sponsor: University of California, San Diego
Start date: 2017-02-17; Completion date: 2020-11-02
Enrollment: 105 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Kawasaki disease (KD) is a self-limited illness that affects the heart blood vessels (coronary arteries) of infants and children and is now the most common cause of acquired heart disease in children. A mixture of proteins from human blood (Intravenous immunoglobulin, IVIG) is a treatment that reduces the rate of the major complication of the disease: a bulging of the wall of the coronary arteries called an aneurysm. However, 10-20% of children are resistant to this treatment and the fever returns. These children have the highest rates of aneurysm formation and thus should be treated aggressively. Unfortunately, there are no guidelines for the best secondary treatment for these resistant patients because the problem has never been adequately studied. Most physicians choose either a second infusion of IVIG or an engineered antibody called infliximab that inactivates a molecule that promotes inflammation. This trial will randomize (assign by chance like the flip of a coin) IVIG-resistant patients to receive either a second IVIG infusion or infliximab and the response to treatment will be compared to learn which treatment stops the fever the fastest. In addition, parents and caregivers will provide observations about their child's response to the different treatments.

Detailed description:
This is a 3-year (2.75-years of enrollment), Phase III, two-arm, randomized, multi-center, superiority treatment study to compare infliximab to a second intravenous immunoglobulin (IVIG) infusion for treatment of persistent or recrudescent fever in children with KD who fail to become afebrile after the first IVIG infusion.

1. Specific aim 1 will test the hypothesis that infliximab will be superior to a second intravenous immunoglobulin (IVIG) infusion for treatment of persistent or recrudescent fever in children with KD who fail to become afebrile after the first IVIG infusion (resistant KD). Cessation of fever (\<38°C rectally or orally) within 24h of initiation of study treatment infusion will be the primary outcome measure.
2. Specific aim 2 will test the hypothesis that infliximab treatment will result in more rapid resolution of inflammation compared to second IVIG as measured by the change in white blood cell count (WBC), absolute neutrophil count (ANC), and high-sensitivity C-reactive protein (hsCRP) concentration between baseline and 24 hours and 2 weeks following study treatment.
3. Specific aim 3 will test the hypothesis that infliximab treatment will result in a reduction from baseline in coronary artery Zworst score of ≥ 0.05 standard deviation units as compared to second IVIG at 2 weeks following study treatment measured by echocardiography.

Arms: arm 1: Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion arm 2: Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours
Interventions: intervention 1: IVIG intervention 2: Infliximab
Intervention descriptions: intervention 1: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours intervention 2: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours

Protocol documents:
Prot_SAP_000.pdf: 
 
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Manual of Operations 
 
 
 
KIDCARE  
(Kawasaki Disease  
Comparative Effectiveness Trial) 
 
 
 
 
October 14, 2019 
 
 
 
 
 
 
 
Jane C. Burns, MD (Co-PI) 
Katherine Kim, PhD (Co-PI) 
Adriana H. Tremoulet, MD, MAS (Safety Officer) 
Samantha Roberts, MS (Program Coordinator) 
Sonia Jain, PhD (Biostatistician) 
 
 


 
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Table of Contents 
1. 
List of investigators .................................................................................................................................. 4 
2. 
Study Overview ........................................................................................................................................ 5 
2A. Overall Objective ..................................................................................................................... 5 
2B. Study Type .............................................................................................................................. 5 
2C. Study Population ..................................................................................................................... 5 
2D. Study Duration ........................................................................................................................ 5 
2E. Primary Outcome ..................................................................................................................... 5 
3. 
Background, Significance, and Rationale ................................................................................................ 6 
3A. Significance ............................................................................................................................. 6 
4. Study design ................................................................................................................................................. 6 
4A. Research Design Overview ....................................................................................................... 6 
4B. Inclusion ................................................................................................................................. 7 
4C. Exclusion ................................................................................................................................ 8 
4D. Study Sites and Target Enrollment ............................................................................................. 8 
4E. Dosing Protocols ..................................................................................................................... 9 
1. Second IVIG ......................................................................................................................................... 9 
2. Infliximab ............................................................................................................................................. 9 
3. Aspirin .................................................................................................................................................. 9 
4F. Discharge from the Hospital ..................................................................................................... 9 
5. Data Collection ........................................................................................................................................... 10 
5A. Tracking Total Number of KD Patients at each Site ................................................................... 10 
5B. Obtaining a REDCap account ................................................................................................. 10 
University of California Active Directory (AD) Account: .................................................................... 10 
Two-Step Authorization: DUO: ............................................................................................................. 10 
Clinical Translations Research Institute (CTRI) forms: ........................................................................ 16 
5C.  REDCap Access Via UCSD Clinical Web Portal (CWP) ........................................................... 16 
5D. Overview of Forms ................................................................................................................ 18 
5E. Eligibility Evaluation Form and Informed Consent .................................................................... 19 
How to complete the Eligibility Evaluation Form in REDCap: ............................................................. 19 
5F. Trial Arms Form-Randomization ............................................................................................. 23 
How to randomize your subject: ............................................................................................................ 23 
5G. Demographics Form .............................................................................................................. 27 
How to complete the Demographics Form in REDCap: ........................................................................ 27 
5H. Study Drug Administration Form ............................................................................................ 30 
How to complete the Study Drug Administration Form in REDCap: ................................................... 30 
5I. Enrollment Temperature Measurement/Temperature Measurement Form ..................................... 33 
How to complete the Enrollment Temperature Measurement/Temperature Measurement Form in 
REDCap: ................................................................................................................................................ 33 
5J. Primary Temperature Outcome/Secondary Temperature Outcome ............................................... 36 
How to complete the Primary Temperature Outcome/Secondary Temperature Outcome Forms in 
REDCap: ................................................................................................................................................ 36 
5K. Laboratory Results Form ........................................................................................................ 39 
How to complete the Laboratory Results Form in REDCap: ................................................................. 39 


 
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5L. Center Echocardiogram Form ................................................................................................. 43 
How to complete the Center Echocardiogram Form in REDCap: ......................................................... 43 
Worst Ever Echo .................................................................................................................................... 46 
5M. Fever Days and Duration of Hospitalization Form ................................................................... 46 
How to complete the Fever Days and Hospitalization Form in REDCap: ............................................. 47 
5N. Concomitant Medication ........................................................................................................ 50 
How to complete the Concomitant Medication Form in REDCap: ....................................................... 50 
5O. Patient Observation Tool ........................................................................................................ 53 
How to complete the Parent Observation Tool Form in REDCap: ........................................................ 54 
5P. Adverse Event Reporting From ................................................................................................ 56 
1. Risks associated with second IVIG treatment .................................................................................... 56 
2. Risks associated with infliximab treatment ........................................................................................ 57 
3. Adverse Events ................................................................................................................................... 57 
4. Serious Adverse Events ...................................................................................................................... 57 
Reporting Unanticipated Problems involving risk to subjects or others (URPs) ................................... 57 
Hemolytic Anemia ................................................................................................................................. 59 
How to complete the Adverse Event Form in REDCap: ....................................................................... 59 
5Q. Protocol Deviations Form ...................................................................................................... 65 
How to complete the Protocol Deviations Form in REDCap: ............................................................... 66 
5R. Study Completion From .......................................................................................................... 68 
How to complete the Study Completion Form in REDCap: .................................................................. 68 
6. Additional Therapy .................................................................................................................................... 71 
6A. Crossover treatment ............................................................................................................... 71 
6B. Management of Treatment-resistant Subjects ............................................................................ 71 
6C. Additional Therapy for Coronary Artery Abnormalities ............................................................. 72 
6D. Allowable concomitant medications ......................................................................................... 72 
7. Privacy and Confidentiality of Data ........................................................................................................... 72 
8. Statistical Considerations ........................................................................................................................... 73 
8A. Power and Sample Size Justification ........................................................................................ 73 
8B. Statistical Analysis Plan ......................................................................................................... 73 
8C. Evaluation of Safety Outcomes ................................................................................................ 75 
9. Data Safety Monitoring Board ................................................................................................................... 75 
References: ................................................................................................................................................... 102 
 


 
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1. List of investigators 
 
Jane C. Burns, MD  
Role: Co-PI 
Professor 
Director, Kawasaki Disease Research Center 
Division of Allergy, Immunology, and Rheumatology 
Department of Pediatrics 
University of California San Diego 
Rady Children’s Hospital San Diego 
jcburns@ucsd.edu 
Page: 858-576-1700, ext. 0 
(w) 858-246-0155 
(m) 858-775-6805 
FAX: 858-246-0156 
 
Katherine Kim, PhD, MBA, MPH 
Role: Co-PI 
Assistant Professor 
Bette Irene Moore School of Nursing 
University of California Davis  
kathykim@ucdavis.edu  
(w): 510-761-5406 
 
Adriana H. Tremoulet, MD, MAS  
Role: Safety Officer 
Associate Professor 
Associate Director, Kawasaki Disease Research Center 
Division of Pharmacology and Drug Discovery 
Department of Pediatrics 
University of California San Diego 
Rady Children’s Hospital San Diego 
atremoulet@ucsd.eduj 
Pager: 858-616-3856 
(w): 858-246-0012 
(m): 858-245-1347 
FAX: 858-246-0156 
 
Sonia Jain, PhD 
Role: Study Biostatistician 
Professor 
Director, Biostatistics Research Center 
Division of Biostatistics and Bioinformatics 
Department of Family and Preventive Medicine 
University of California San Diego 


 
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2. Study Overview 
2A. Overall Objective  
The goal of this study is to determine whether infliximab or a second IVIG infusion abrogates fever faster 
and is associated with fewer adverse events in IVIG-resistant Kawasaki disease (KD) patients.  
2B. Study Type 
This is a Phase III, two-arm, randomized, multi-center, treatment study. 
2C. Study Population 
Infants and children with acute KD who are IVIG-resistant (fever T ≥38°C orally or rectally or 37.5°C 
axillary/ T ≥100.4°F orally or rectally or ≥ 99.5°F axillary) between 36 hours and 7 days after the end of 
the first IVIG infusion without other likely cause. 
2D. Study Duration 
 4 years  
2E. Primary Outcome  
1) Afebrile at 24h after initiation of study treatment and remains afebrile with no recurrence of fever 
related to KD in the first 7 days after discharge.  
2F. Secondary Outcomes  
1) Afebrile at 24h following completion of infusion of study treatment (i.e., infliximab or IVIG) and 
remains afebrile until discharge with no recurrence of fever related to KD in first 7 days after 
discharge. 
2) Number and severity of therapy-related adverse events according to treatment arm as adjudicated by 
the Adverse Events Committee. 
3) Change in white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hgb), 
platelet count, and C-reactive protein (CRP, mg/dl) concentration between baseline (pre-IVIG at 
diagnosis), 24 hours (± 2 hours) post-end of study treatment and 5-18 days  following completion of 
study treatment  
4) Change in erythrocyte sedimentation rate (ESR) between pre-IVIG at diagnosis and 5-18 days 
following completion of study treatment 
5) Change in ZMax score (defined as the largest internal diameter of either the right coronary or left 
anterior descending arteries normalized for body surface area and expressed as standard deviation 
units from the mean) between baseline (first echocardiogram on admission) and 5-18 days  
following completion of study treatment echocardiograms  
6) Total number of fever days (24 hour period with a T≥38.0°C orally or rectally or ≥37.5°C axillary/ 
T ≥100.4°F orally or rectally or ≥ 99.5°F axillary) from enrollment  
7) Duration of hospitalization  
8) Number and severity of study treatment infusion reactions 
9) Requirement for additional anti-inflammatory therapies after crossover failure 
10) Comparison of patient/parent-reported outcomes (PROs) by study arm through the use of a parent 
observation tool to record discomfort, psychosocial concerns, and other experiences of treatment 
during the child’s in-hospital stay and outpatient course.   


 
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3. Background, Significance, and Rationale 
3A. Significance 
Kawasaki disease (KD) is a self-limited vasculitis of unknown etiology that is the most common cause of 
acquired heart disease in children (Newburger et al. 2016). Intravenous immunoglobulin (IVIG) reduces the 
incidence of coronary artery aneurysms (CAA) from 25% to approximately 5% (Newburger et al. 1986). 
However, for the 10-20% of IVIG-resistant patients (defined as having T≥ 38.0°C at least 36h following 
the end of the IVIG infusion), there is no evidence-base to guide treatment and this group has an increased 
risk of coronary artery aneurysms. In our study of 362 consecutive KD patients, 9 of 60 IVIG-resistant 
patients (15%) versus 9 of 302 (3%) developed CAA (Tremoulet, Best et al. 2008). Recent data from Japan 
suggests that the rates of IVIG-resistance have risen from 7% in 2003 to 23% in 2014 with a concomitant 
increase in CAA (Kibata, Suzuki et al. 2016). 
 
3B. Rationale   
 
There is clinical equipoise regarding the best treatment for IVIG-resistant patients and either a second 
infusion of IVIG or infliximab (a monoclonal antibody that blocks the pro-inflammatory cytokine tumor 
necrosis factor (TNFα) is the most common second treatment (Sundel, Burns et al. 1993, Burns, Capparelli 
et al. 1998, Burns, Best et al. 2008, Son, Gauvreau et al. 2011). Some centers also treat with steroids (Yang, 
Liu et al. 2015). The American Heart Association (AHA) KD guidelines assign an Evidence level of C 
(Consensus opinion of experts) to re-treatment with either second IVIG or infliximab (Newburger, 
Takahashi et al. 2004). However, the stakes are high for this subgroup of patients as CAA due to persistent 
inflammation constitutes permanent damage to the arterial wall with an associated risk of myocardial 
infarction, arrhythmias, or sudden cardiac death (Kato, Sugimura et al. 1996, Gordon, Daniels et al. 2016). 
 
For this trial, the dose of infliximab will be 10 mg/kg IV. A Phase III clinical trial of adjunctive primary 
therapy with infliximab at 5 mg/kg demonstrated that infliximab is safe and well-tolerated even in infants 
less than 6 months of age (Tremoulet, Jain et al. 2014). Further study of KD patients enrolled in this trial 
demonstrated that pre-treatment soluble TNFα receptor 1 (sTNFR1) levels are elevated in acute KD and are 
higher in KD patients with CAA compared to those with normal CA. At 24 hours following infusion of 
infliximab 5 mg/kg, KD patients with CAA had lower levels of free (unbound) infliximab compared to 
those with normal CA. These data suggest that 5 mg/kg of infliximab may be insufficient for many KD 
patients and thus a single dose of 10 mg/kg of infliximab is warranted for this study. Infliximab at a dose of 
10 mg/kg has been used at RCHSD for the treatment of 88 acute KD patients with either CAA or IVIG-
resistance with no adverse events related to this therapy.  
 
4. Study design  
 
4A. Research Design Overview 
KIDCARE is a 4-year (3.75-years of enrollment), Phase III, two-arm, randomized, multi-center, treatment 
study to compare infliximab to a second intravenous immunoglobulin (IVIG) infusion for treatment of 
persistent or recrudescent fever in children with KD who fail to become afebrile after the first IVIG 
infusion at collaborating clinical sites (see Appendix A). 


 
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4B. Inclusion 
1) 4 weeks to < 18 years of age,  
2) Meets American Heart Association (AHA) criteria for KD by one of the following:  
a. Four of five clinical KD criteria (see Table 1) 
b. Meets 2017 AHA criteria for incomplete KD  (see Table 2)  
3) Fever by parental history for 3 to 10 days prior to initial IVIG treatment 
4) Fever (T ≥38°C orally or rectally or ≥37.5°C axillary/ T ≥100.4°F orally or rectally or ≥ 99.5°F 
axillary) between 36 hours and 7 days after end of the first IVIG infusion that is more likely than not 
related to KD in the opinion of the Site PI or Co-investigator 
 
Table 1. Diagnostic criteria for KD with CAA (Adapted from American Heart Association 
2017 guidelines) 
KD standard clinical criteria: 
 Bilateral conjunctival injection 
 Changes of the mucous membranes of the upper respiratory tract: injected pharynx, 
injected, fissured lips, strawberry tongue 
 Changes of the peripheral extremities: peripheral edema, peripheral erythema, periungual 
desquamation 
 Polymorphous rash 
 Cervical adenopathy >1.5 cm 
             
 
 
 


 
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Table 2.  AHA Criteria for incomplete KD (McCrindle et al., Circulation, 2017) 
 
(1) In the absence of a “gold standard” for diagnosis, this algorithm cannot be evidence based but rather represents the informed 
opinion of the expert committee. Consultation with an expert should be sought any time assistance is needed. (2) Clinical findings 
of Kawasaki disease are listed in Table 3. Characteristics suggesting that another diagnosis should be considered include 
exudative conjunctivitis, exudative pharyngitis, ulcerative intraoral lesions, bullous or vesicular rash, generalized adenopathy, or 
splenomegaly. (3) Infants ≤6 months of age are the most likely to develop prolonged fever without other clinical criteria for 
Kawasaki disease; these infants are at particularly high risk of developing coronary artery abnormalities. (4) Echocardiography is 
considered positive for purposes of this algorithm if any of 3 conditions are met: Z-score of left anterior descending coronary 
artery or right coronary artery ≥2.5; coronary artery aneurysm is observed; or ≥3 other suggestive features exist, including 
decreased left ventricular function, mitral regurgitation, pericardial effusion, or Z scores in left anterior descending coronary 
artery or right coronary artery of 2 to 2.5. (5) If the echocardiogram is positive, treatment should be given within 10 days of fever 
onset or after the tenth day of fever in the presence of clinical and laboratory signs (C-reactive protein [CRP], erythrocyte 
sedimentation rate [ESR]) of ongoing inflammation. (6) Typical peeling begins under the nail beds of fingers and toes. ALT 
indicates alanine transaminase; and WBC, white blood cells 
 
4C. Exclusion 
1) Patient treated with infliximab or steroids for present illness (e.g. RAISE protocol) (NB. patients who 
received oral steroids as outpatients prior to KD diagnosis (e.g. for suspected allergic reaction) but who 
otherwise qualify for the study will not be excluded) 
2) Known prior infection with tuberculosis, coccidiomycosis, or histoplasmosis. 
3) Household member with active TB. 
4) Use of a TNF-α  blocker within the 3 months prior to enrollment 
5) Have any chronic disease, except asthma, atopic dermatitis, autism or controlled seizure disorder  
6) Patient has a history of hypersensitivity to infliximab or antibodies derived from murine cells 
4D. Study Sites and Target Enrollment 
Subjects will be enrolled at participating sites over 3.75 years and randomized to infliximab or 2nd IVIG. 
Target enrollment will be 112 subjects (56 subjects/arm). We anticipate an enrollment of 0-15 subjects/year 
per participating site. 


 
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4E. Dosing Protocols 
1. Second IVIG  
All subjects randomized to receive a second dose of IVIG as their first study treatment will receive 2g/kg 
IV over 8-12 hours. The start and stop times, as well as the brand of IVIG administered, will be recorded 
on the Study Drug Administration form on REDCap. Premedication is not recommended but its use will 
be at the discretion of the site PI. If premedication is used, this drug name, dose, route, and time 
administration must be recorded on the Concomitant Medication form on REDCap. 
2. Infliximab 
All subjects randomized to receive infliximab will receive 10 mg/kg intravenously over a minimum of 2 
hours. The start and stop times will be recorded on the Study Drug Administration form on REDCap. 
Premedication is not recommended but its use will be at the discretion of the site PI. If premedication is 
used, this drug name, dose, route, and time of administration must be recorded on the Con Med CRF. The 
FDA does not require a PPD or Quantiferon® testing prior to single dose administration of infliximab to 
KD patients given that the majority are anergic during the acute illness. A CXR is no longer a requirement 
prior to single dose infliximab administration for treatment of KD. 
N.B. Documentation of a concomitant viral infection by PCR or other methods should not be considered a 
contraindication to receiving infliximab.  
3. Aspirin 
All subjects should receive 30-50 mg/kg/day divided every 6 hours following randomization until the 
time of discharge. Centers may use 80-100 mg/kg/day but are encouraged to adopt the more moderate ASA 
dosing of 30-50 mg/kg/day. Upon discharge or in the event of initiation of dual anti-platelet therapy in a 
subject with aneurysms, the dose of aspirin (ASA) will be lowered to 3-5 mg/kg/day and administered as 
either 40.5 mg or 81 mg aspirin once daily.  ASA will be continued at least until the end of the study 
(follow-up visit) and discontinued thereafter at the center PI’s discretion. This medication will be recorded 
on the Concomitant Medication form on REDCap. It will also be recorded on the Temperature 
Measurement form.  You will need to record the date and time of the Aspirin given before the temperature 
was taken.   
4F. Discharge from the Hospital 
A subject who is afebrile at 24h after the completion of study drug administration may be discharged from 
the hospital as long as 24 hours have elapsed from the completion of the study treatment to ensure that 
outcome measures and laboratory studies are obtained. 
 
4G. Temperature measurement by parents during first 7 days after discharge 
Sites will receive thermometers to give to the parents at the time of discharge for at home measurement of 
axillary temperatures once/day for the first 7 days following discharge. The daily Twilio contact will ask 
the parent for the first 7 days only if their child had a fever and the answer will be recorded. The parent will 
be prompted each day for the first 7 days to contact their study doctor if a fever is documented (T ≥37.5°C / 
T ≥ 99.5°F axillary). Causality of any recurrent fever will be adjudicated by the site PI and will be 
designated as related (more likely than not) or unrelated to KD. 
 
 
 


 
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5. Data Collection 
 
***All data from hospitalization must be entered into REDCap within a week of patient discharge 
and all data from follow-up visit no later than one week after the visit*** 
 
All Forms are located in Appendix C. 
5A. Tracking Total Number of KD Patients at each Site 
Each site will be responsible for maintaining a log of the total number of KD patients seen at their site 
during the study period. For each site, this log will need to be maintained from the time the site was opened 
for enrollment in KIDCARE until the closure of enrollment. It will include the date of KD onset for each 
patient seen at your site. This information will NOT be entered into the REDCap database but will be 
requested by the Program Manager at Coordinating Center, Samantha Roberts (sroberts@ucsd.edu), via 
email every month. 
5B. Obtaining a REDCap account 
Each approved site’s research team needs to get access to the KIDCARE REDCap database.   Once you 
have been IRB approved, Samantha will set up a call with each member of your team to start the process of 
access.  Below are the steps that need to be taken: 
University of California San Diego (UCSD) Active Directory (AD) Account:  
Samantha will need to set up a call with each individual member of the research team.  To get an AD 
account with UCSD, each member will have to give Samantha the following information: the last 4 of their 
Social Security Number, month of birth, and day of birth. This information is submitted securely to UCSD.  
Each member will then receive an email from UC Health Service Management that will include their AD 
account username and their temporary password.  All passwords much be changed immediately. 
 
How to change your UCSD AD account password 
 
1. Go to -> https://password.ucsd.edu/ 
2. Choose “I know my current AD password and would like to change it” 
3. Your password needs to be: 
a. At least 7 characters long 
b. Have characters from at least 3 of the following 4 categories: uppercase, lowercase, 
numbers, and symbols  
c. Cannot contain any part of your username 
d. Cannot resemble any single work or name 
Two-Step Authorization with DUO:  
Access to the KIDCARE REDCap database requires two-step authorization using DUO.  It is 
recommended that the DUO App is downloaded onto the user’s phone.  You do not have to use DUO 
mobile app for two-step authorization, it is just recommended.  
 
 
 
 


 
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Install DUO App on a Mobile Phone: 
Before starting, note that for Apple you'll need to be running iOS 10.0 or greater, and for Android, you'll 
need to be on Android 6.0 or greater.  
 
1. Find the Duo Mobile app. Note that other apps may appear, so be sure you're installing Duo Mobile 
with the green logo. 
 
 
  
2. When you open the app, you'll probably want to allow Duo to send notifications. This will lead to 
the most seamless experience using two-step login. Otherwise, each time you log in you'll have to 
open the app to approve.  
 
 
  
3. Get ready to add your account in the Duo app. You can either tap "ADD ACCOUNT" or tap the 
plus symbol in the upper right corner. 
 


 
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4. The Duo app will need to access your camera to complete the registration process (see below). 
Allow the access, then put the phone down momentarily to continue to the device registration 
interface. 
 
   
 
 
 
 
 
 
 
 
 
 


 
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Register a Mobile Phone for Two-Step Login 
 
1. You will need to complete the registration page: https://healthapps.ucsd.edu/duo/duo-app.asp  using 
your AD username login and password. When you see the screen below, click "Start setup" to get 
going. 
 
  
2. Choose the type of device to add. Using a mobile phone as your primary device is highly 
recommend. Select the radio button and click "Continue." 
 
 
 
3. Enter the mobile phone's number, click the check box to confirm, and click "Continue." 
 
 
 
 
 
 
  


 
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4. Choose the type of device you're registering, and click "Continue." 
 
 
 
5. You'll be prompted to install the Duo mobile app (if you haven't already). See instructions above. 
Once the app is installed, click "I have Duo Mobile installed." 
  
  
 
 
 
 
 
 
 
 


 
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6. Follow the on-screen instructions to open your Duo app and scan the barcode that appears on 
screen. You may need to grant Duo permission to access your camera. 
            This is the key step that ties your identity to your device! 
 
  
7. Congrats! You've enrolled your device. 
  
 


 
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Clinical Translations Research Institute (CTRI) forms:  
Once the research team members receive their AD account username, Samantha will also receive this 
username.  She will submit it to the CTRI at UCSD, who will then send a REDCap User Access Request 
form that will need to be completed and electronically signed.  The following information is requested on 
the form: 
a) First, Middle, Last Name, and Title 
b) Telephone # (include country code if outside the U.S.) 
c) FAX # (include country code if outside the U.S.) 
d) Department 
e) Division (Hospital/Center Affiliation) 
 
5C. REDCap Access Via UCSD Clinical Web Portal (CWP)  
Once research team members have an AD account and have set up two step authorization with DUO, they 
can then access the REDCap. 
1. Go to https://cwp.ucsd.edu  
 
2. You will log in using your AD account username and password.  
 
 
 
 
 
 
 


 
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3. You should receive a login request on your phone from the Duo Mobile App. 
 
 
 
4. Open the Duo Mobile App on your phone and approve the login request. 
 
 
 
5. Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP): 
 
 
 
 
 
 
 
 
 


 
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6. Select the KD REDCap icon 
 
 
 
7. The REDCap database will be opened up in another web page.  You will use the same username 
and password for this REDCap as you used for the iDASH REDCap. 
 
5D. Overview of Forms 
Form Name 
Study Event 
Eligibility Evaluation 
Enrollment* 
Trail Arms From 
Enrollment* 
Demographics 
Enrollment* 
Study Drug Administration 
Enrollment* 
Enrollment Temperature Measurement 
Enrollment 
Temperature Measurement 
24 hours post initiation of study tx, 24 hours post completion of 
study tx 
Primary Temperature Outcome 
24 hours post initiation of study tx 
Secondary Treatment Outcome 
24 hours post completion of study tx 
Laboratory Results  
Enrollment, 24 hours post completion of study tx, Follow-Up 
Visit 
Center Echocardiogram 
Enrollment*, Follow-Up, Other Data 
Baseline Observation tool 
24 h post completion of study tx 
8-hour Observation tool 
24 hours post completion of study tx 
16-hour Observation Tool 
24 hours post completion of study tx 
24-hour Observation Tool 
24 hours post completion of study tx 
Crossover Temperature Measurement 
Crossover of study tx 
Crossover Study Drug Administration 
Crossover of study tx 
Crossover Laboratory Results 
Crossover of study tx 
Protocol Deviation Reporting Form 
During Study (as applicable) 
Adverse Event Reporting Form 
During Study (as applicable) 
Study Completion Form 
Follow-Up Visit 
Fever Days and Duration of Hospitalization 
Other Data 
Concomitant Medications 
Other Data 
* This study event name is associated with the REDCap event name and does not indicate when this data 
will be collected.  Non-eligible patients are not enrolled into the study and the information gathered about 
why they did not enroll into the study is de-identified.   


 
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5E. Eligibility Evaluation Form and Informed Consent 
Study participation will be offered without regard to age, sex, or ethnic background. Child assent will be 
obtained for all study patients ≥ 7-12 yrs. and adolescent assent will be obtained for patients 13-17 yrs. 
Recruitment of human subjects with written Informed Consent will be obtained by study personnel in the 
hospital inpatient units. There are occasions when no study personnel are available in the hospital, in which 
case one of the co-investigators is contacted by telephone.  The Parent (child/ adolescent if applicable) is 
provided with the written consent form and HIPAA authorization by hospital personnel and the co-
investigator reviews the written informed consent document(s) over the phone and answers any questions.  
The parent (child/adolescent if applicable) then signs and dates the consent document (s) and the witness 
signature is obtained at a later time from the co-investigator who obtained the informed consent.  The 
Parent (child/ adolescent if applicable) will be provided with the signed written consent form and HIPAA 
authorization. 
 
Screen Fails:  All subjects who meet the AHA criteria for complete or incomplete KD and who had a 
fever (T ≥38°C orally or rectally or 37.5°C axillary/ T ≥100.4°F orally or rectally or ≥ 99.5°F axillary) 
between 36 hours and 7 days after the end of the first IVIG infusion without other likely cause will be 
included in the REDCap database. Some KD subjects who have a fever between 36 hours and 7 days 
after the end of the first IVIG infusion will not be eligible for the study because the subject did not meet 
entry criteria or the family refused to participate in this study.  These subjects who have been screened for 
study participation, will have their screening information entered into the eligibility evaluation form 
REDCap without consent being obtained. This de-identified information is collected to understand why 
patients either were not eligible or refused participation for the study.  All the information entered into the 
REDCap database is de-identified. 
How to complete the Eligibility Evaluation Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.   
8) Under My Projects, Choose KIDCARE Trial 2017 
9) On the left side of the REDCap portal, you will see a section labeled Data Collection 
10)  Click on the Record Status Dashboard under this section. 
 
 
 
 
 
 
 
 
 
 
 


 
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11) Choose the next subject that needs to be completed. To do this you will choose the subject ID that 
has the first RED circle.  
 
 
12) Then click on that subjects study ID  
             
 
 
 
13) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the Enrollment 
column and next to the Eligibly Evaluation form that you need to complete  
 


 
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14) When you click on the circle you will be taken to the Eligibly Evaluation form 
 
 
 


 
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15) Answer all the questions within the Eligibility Evaluation form. Make sure you answer the last 
question in this form correctly, which is: Does the patient qualify for the study?  This question 
will determine if you will be able to randomize your subject   
16) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record. 
 
 
 


 
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17)   From here you will be directed back to the subjects study dashboard. The circle next to the 
Eligibly Evaluation form should be Green. 
 
            
  
 
5F. Trial Arms Form-Randomization 
Once eligibility and consent are confirmed and the eligibility evaluation form is completed, subjects will be 
assigned to a treatment arm (Infliximab or IVIG) by the REDCap online randomization module according 
to a pre-specified randomization scheme stratified by center and then sex (male/female) and age 
(dichotomous variable >12 months or ≤ 12 months) via a randomly permuted block design. The 
randomization sequence has been generated by the Biostatistics team using the software R (version 3.3.2).   
How to randomize your subject: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section. 
 
 
 
 
 


 
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10) Choose the subject that needs to be randomized. To do this you will choose the subject ID that has 
the circle under the first from as GREEN but the circle under the Trial Arms form as UNFILLED.   
 
 
 
11) Then click on that subjects study ID  
 
           
 


 
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12) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the Enrollment 
column and next to the Trial Arms form you need to complete 
 
 
13) Complete the Trial Arms form with the date, your site, sex of subject, and age category of subject 
(Less than or equal to 12 months or Greater than 12 months) 
 
 
14) Click the Randomize button next to the Randomized Treatment Arm field 
           
 
 
15) A window will pop up Please check the data you entered. Make sure your site number is 
correct (the site number you picked should match the first two numbers of your subject ID). 
16) Once you check that the data you entered is correct, click the Randomize button.  
 


 
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17) Your subject has been randomized to either infliximab or IVIG.  This will show up Randomized 
Treatment Arm field 
 
 
 
 
 
 
 
 
 
 
 


 
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18) Once you have completed this form, change the status of the form Incomplete to Complete and then 
click Save Record 
     
 
 
          
 
19)   From here you will be directed back to the subjects study dashboard. The circle next to the Trial 
Arms form should be GREEN 
 
 
 
5G. Demographics Form 
Data collected in the form include: 
a) Patient's age in years at KD onset rounded to nearest 0.1 years, sex, self-reported ethnicity of each 
biologic parent  
b) Illness day at 1st IVIG treatment (first day of fever = Illness Day 1) and illness day at 
randomization (each day is the 24h period from 12:01 am to 12:00 pm). Example: For a patient who 
is admitted at 6 pm on Illness Day 5 but starts treatment at 1 is that night, the Illness Day at 1st 
IVIG treatment is Illness Day 6. 
How to complete the Demographics Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 


 
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5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10)  Click the subject ID that needs to be completed.   
 
            
 
 
 
 
 
 
 
 
 
 


 
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11) You will then be taken to this subject’s REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the Enrollment 
column and next to the Demographics form you need to complete 
 
            
 
 
12) When you click on the circle you will be taken to the Demographics form 
 
 
 
13) Answer all the questions within the Demographics form 
 
 
 
 


 
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14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record 
 
 
 
 
 
15)   From here you will be directed back to the subjects study dashboard. The circle next to the 
Demographics form should be GREEN 
 
  
 
5H. Study Drug Administration Form  
Name, brand, dose, start time/date and stop time/date of 1st study treatment and 2nd study treatment if 
subject crossed over to other study treatment. 
How to complete the Study Drug Administration Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal,you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section 


 
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10) Click the subject ID that needs to be completed.   
 
          
 
 
 
11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the column 
Enrollment and next to the Study Drug Administration form you need to complete.  
 
          
 
 
 
 
 


 
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12) When you click on the circle you will be taken to the Study Drug Administration form 
 
 
 
13) Answer all the questions within the Study Drug Administration Form  
14) Once you complete the form, change the status of the form Incomplete to Complete and then click 
Save Record 
 
 
 
 
 
 
 
 
 
-This section will change 
depending on which 
treatment your subject was 
randomized to.  This 
subject was randomized to 
IVIG, so the dosing for 
IVIG appears.  If subject 
was randomized to 
infliximab then the 
infliximab dosing would 
appear 
-The amount of drug 
administered also depends 
on which drug your subject 
was randomized to.  If 
IVIG then dose is recorded 
in grams, if infliximab then 
dose recorded in mg 


 
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15) From here you will be directed back to the subjects study dashboard. The circle next to the Study 
Drug Administration form should be GREEN 
 
 
****If the subject crosses over to the other study treatment, repeat steps 1-10 for the Crossover Study 
Administration form located under the Crossover of study tx column.   
5I. Enrollment Temperature Measurement/Temperature Measurement Form  
The preferred routes for measuring the temperature are oral and rectal. A fever will be considered T ≥38°C/ 
T ≥100.4°F rectally or orally. Sites that are unable to obtain core temperatures via these routes can use 
axillary temperatures as an alternative with T ≥ 37.5°C/ T ≥ 99.5°F   axillary considered to be a fever. 
While other methods can be used (temporal wand, tympanic temperature, etc.) to monitor patients, 
temperature time points (see below) required for the study MUST BE DOCUMENTED BY EITHER 
ORAL, RECTAL OR AXILLARY ROUTES.  If another method was used for a key time point, enter that 
value with a comment on methods. If you do not use one of the preferred methods, completed the Protocol 
Deviation form on REDCap. Please work with your nursing staff to explain the importance of correct 
temperature measurement. 
 
Temperature, route of measurement, date, and time (24h clock) for the following time points: 
a. Qualifying temperature at study entry and route (Centigrade or Fahrenheit) 
b. 24 hours (±2h) from initiation of study treatment;  
c. 24 hours (±2h) from completion of study treatment 
d. If 2nd  study treatment administered, i-iii above for 2nd study treatment 
 
** If you only have a temperature that is out of the window, enter the temperature that is closest to the 
desired window and enter the time. Complete the Protocol Deviation form on REDCap. 
How to complete the Enrollment Temperature Measurement/Temperature Measurement 
Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  


 
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9) Click on the Record Status Dashboard under this section.           
 
 
10)  Click the subject ID that needs to be completed.   
 
           
 
 
 
11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the column for 
the time point (below) you are entering the data for and next to the Enrollment Temperature 
Measurement or Temperature Measurement form you need to complete 
 
The Enrollment Temperature Measurement form is its own form to record the qualifying 
temperature at study entry and route. 
 
The time points for the Temperature Measurement Form 
a. 24 hours post initiation of study tx 
b. 24 hours post completion of study tx 
 


 
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12) When you click on the circle you will be taken to the Enrollment Temperature Measurement or 
Temperature Measurement form. 
 
 
 
13) Answer all the questions within the Enrollment Temperature Measurement or Temperature 
Measurement form  
14) Once you complete the form, change the status of the form Incomplete to Complete and then click 
Save Record. 
 
           
 
 


 
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15) From here you will be directed back to the subjects study dashboard. The circle next to the 
Enrollment Temperature Measurement or Temperature Measurement form you completed should 
be green. 
 
 
 
 
****If the subject crosses over to the other study treatment, repeat steps 1-10 for the Crossover 
Temperature Measurement form located under the Crossover of study tx column.   
5J. Primary Temperature Outcome/Secondary Temperature Outcome 
These forms are completed at 24 hours post initiation of study treatment (primary) and 24 hours post 
completion of study treatment (secondary).  These two forms are VERY important and need to be 
completed.   They are the main outcomes of the study, asking if the subject was afebrile at these two time 
points. 
 
How to complete the Primary Temperature Outcome/Secondary Temperature Outcome 
Forms in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 


 
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7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section.           
 
 
10)  Click the subject ID that needs to be completed.   
 
           
 
 
11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the column for 
the time point (below) you are entering the data for and next to the Primary Temperature 
Outcome/Secondary Temperature Outcome form you need to complete 
              
 
 


 
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12) When you click on the circle you will be taken to the Primary Temperature Outcome/Secondary 
Temperature Outcome form 
 
 
 
 
 
13) Answer the question within the Primary Temperature Outcome/Secondary Temperature Outcome 
form  
14) Once you complete the form, change the status of the form Incomplete to Complete and then click 
Save Record. 
 
           
 
 
 
 
 
 
 
 
 
 


 
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15) From here you will be directed back to the subjects study dashboard. The circle next to the Primary 
Temperature Outcome/Secondary Temperature Outcome form you completed should be green. 
 
 
 
5K. Laboratory Results Form  
White blood count (WBC), absolute neutrophil count (ANC), hemoglobin (Hgb), platelet count, C-reactive 
(CRP, mg/dL) levels at following time points:  
a. Pre-IVIG at diagnosis  
b. 24 hours (± 2 hours) post-completion of study treatment  
c. 5- 18 days following the completion of study treatment (follow-up visit) 
 
Erythrocyte sedimentation rate (ESR) at the following time points: 
a. Pre-IVIG at diagnosis 
b. 5- 18 days following the completion of study treatment (follow-up visit)  
 
How to complete the Laboratory Results Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section. 


 
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10) Click the subject ID that needs to be completed.   
 
         
 
 
 
11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the column for 
the time point (below) you are entering the data for and next to the Laboratory Results form you 
need to complete 
 
The time points for the Laboratory Results form 
a. Enrollment (pre-IVIG at  diagnosis) (if multiple CBCs were performed prior to 
administration of IVIG, choose the CBC closest to time and date of 1st IVIG treatment 
b. 24 hours (± 2 hours) post-completion of study treatment  
c. 5- 18 days following the completion of study treatment 
 
*** Erythrocyte sedimentation rate (ESR) completed at a and c above 
 
         


 
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12) When you click on the circle you will be taken to the Laboratory Results form  
 
 
 


 
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13) Answer all the questions within the Laboratory Results form 
14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record. 
 
 
 
 
 
15) From here you will be directed back to the subjects study dashboard. The circle next to the 
Laboratory Results form should be GREEN 
 
 
 


 
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****If the subject crosses over to the other study treatment, repeat steps 1-10 for the Crossover Laboratory 
Results form located under the Crossover of study tx column.   
5L. Center Echocardiogram Form 
An echocardiogram will be performed at the following time points per standard of care:  
i. 
During initial hospitalization at the time of diagnosis (If multiple 2-D echoes are obtained on a 
given patient prior to diagnosis, then the echo closest to the time of the first IVIG infusion 
should be used on Echocardiogram Form ) 
ii. 
Capturing the worst ever echo between echo closest to 1st IVIG and echo at follow-up visit 
iii. 
5-18 days following the completion of study (follow-up visit) 
 
2-D transthoracic echocardiograms (2-D Echo) will be performed on all KD subjects according to a 
standardized protocol recommended by the Pediatric Heart Network and the AHA. 2-D Echo will be 
performed at KD diagnosis (preferably within 24h of first IVIG infusion prior to study enrollment) and 
again at two weeks (± 4 days) following enrollment. Sedation for children younger than 3 years is 
recommended. The patient’s height and weight and internal lumen diameters in millimeters of the left main 
(LMCA), proximal LAD, circumflex, and proximal and mid RCA will each be measured and recorded on 
the CRF. Dimensions of the LMCA, proximal LAD, circumflex, and proximal RCA will be adjusted for body 
surface area and expressed in standard deviation units (Z-scores) at the Coordinating Center.  
 
Weight of subject should be measured with shoes off.  We recommend that height is measured by a nurse 
and confirmed by a second nurse using a stadiometer. 
How to complete the Center Echocardiogram Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section. 
        
 
 


 
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10)  Click the subject ID that needs to be completed.   
 
         
 
 
 
11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the column for 
the time point (below) you are entering the data for and next to the Center Echocardiogram form 
you need to complete 
 
The time points for the Echocardiogram Form 
a. Enrollment (pre-IVIG at  diagnosis) 
b. 5-18 days following the completion of study treatment (follow-up visit) 
c. Other data entry 
         
          
 
 
 
 
 
 
 
 
 


 
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12) When you click on the circle you will be taken to that Center Echocardiogram form 
 
 
 
13) Answer all the questions within the Center Echocardiogram form 
14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record 
 
 
 
 
 


 
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15) From here you will be directed back to the subjects study dashboard. The circle next to the Center 
Echocardiogram form should be GREEN 
 
 
Worst Ever Echo  
If multiple 2-D echoes are obtained after the first IVIG and prior to the 2-week visit, then the largest 
dimension in mm of the LMCA, RCA, LAD and circumflex should be recorded on the CRF entitled Center 
Echocardiogram form located under Other Data column in REDCap ‘”. If only two 2-D echoes are 
performed (at diagnosis and again at follow-up visit), then form echo at other should not be completed.  
 
            
 
5M. Fever Days and Duration of Hospitalization Form 
Total Fever Days and Duration of Hospitalization data are only collected once on the form located under 
the Other Data column in REDcap.  Data collected in the form include: 
 
a) Total number of fever days (24 hour period with a T ≥38°C orally or rectally or ≥37.5°C 
axillary/ T ≥100.4°F orally or rectally or ≥ 99.5°F axillary) from the time of start of infusion 
of first study treatment. A day is from 12:01 am to 12:00 midnight. Example: If the patient 
starts first study treatment at 1:00 am and becomes afebrile at 11:00 pm that night, then that 
is one fever day. If fever returns two days later at 1:00 am and the patient receives second 
study treatment and becomes afebrile at 11:00 pm that night, then this counts as another 
fever day.  The total number of fever days this patient will have had is 2. 


 
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b) Duration of hospitalization following randomization  (count number of days from 
randomization; each 24h-period from 12:01 am to 12-midnight counts as one calendar day) 
 
How to complete the Fever Days and Hospitalization Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section. 
           
 
 
10)  Click the subject ID that needs to be completed.   
 
            
 


 
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11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under Other Data 
column and next to the Fever Days and Duration of Hospitalization form you need to complete.  
         
             
 
 
12) When you click on the circle you will be taken to that Fever Days and Duration of Hospitalization 
form. 
 
            
 
 
 


 
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13) Answer all the questions within the Fever Days and Duration of Hospitalization Form 
14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record. 
 
 
 
 
15) From here you will be directed back to the subjects study dashboard. The circle next to the Fever 
Days and Duration of Hospitalization form should be GREEN 
 
 
 


 
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5N. Concomitant Medication 
Name, dose, date, time and reason for all concomitant medications taken while on the study.  Aspirin 
medication will be reported in this form. You can include up to 50 concomitant medications. Please do not 
include topical medication.  If a medication is prescribed to be taken as needed (i.e. Tylenol), only include 
the time it was administered, each administration will be its own entry.  
How to complete the Concomitant Medication Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section. 
            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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10)  Click the subject ID that needs to be completed.   
           
 
 
11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the Other Data 
column and next to the Concomitant Medication form you need to complete.    
 


 
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12) When you click on the circle you will be taken to the Concomitant Medication form  
 
 
 
13) Answer all the questions within the Concomitant Medication Form 
14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record. 
 
 
 
 
 
15) From here you will be directed back to the subjects study dashboard. The circle next to the 
Concomitant Medication form should be GREEN 
If you have more than 1 
concomitant medication, 
answer yes to this question.  All 
the question will appear again 
for an additional entry. 


 
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5O. Patient Observation Tool 
After discharge subjects will be monitored for 2 weeks to evaluate for adverse events. The UC Davis team 
(Kathy Kim and Sakib Jalil) developed an instrument that will be presented as a survey either via email to 
the parents/legal guardians. Parents/legal guardians will have the option to choose between paper or email 
as their preferred way of reporting. Their preference will be recorded on p. 6 of the observation tool form in 
Appendix B. During the 2 weeks following discharge, parents/legal guardians will be prompted to complete 
the survey once each day. Any medical conditions reported by the parents (e.g. recurrent fever, 
arthritis/arthralgia interfering with ambulation, new-onset rash) will prompt a message to the parent to 
contact their study doctor. A reminder message is included in the daily contact for the first week only after 
discharge reminding parents to call the study physician if fever has recurred. 
 
Name of forms: 
a) Baseline Observation Tool (Start of Study Treatment) 
b) 8-hour Observation Tool 
c) 16-hour Observation Tool 
d) 24-hour Observation Tool 
 
Parents and legal guardians will complete the Parent Observation Tool to record observations about their 
child. The paper copy of the form must be given to the responsible adult by the site study doctor at the time 
of randomization. The parent/guardian will complete this form at four times during the first 24-hour period 
that their child is in the study: 
 
The four time points for completion of the observation tool while in the hospital are: 
1. Before start of study treatment 
2. Around 8 hours after start of 1st study treatment 
3. Around 16 hours after start of treatment 
4. Around 24 hours after start of treatment. 
If a child receives a second study treatment as a cross-over in the protocol, the parent/legal guardian will 
complete the tool for an additional 24 hours. 
1. Around 8 hours after start of second study treatment 
2. Around 16 hours after start of second treatment 
3. Around 24 hours after start of second treatment 
 
The observation tool is attached as Appendix B.  Note that there are 7 pages to the tool.  Provide pages 1-6 
to the parent.  Page 7 is an example of the monitoring questions that will be collected at home and is for the 
study team reference only. If you have any questions about the this observation tool you can contact the UC 
Davis team by calling Katherine Kim at 510-761-5406 or emailing Katherine at kathykim@ucdavis.edu. 
 
The parent should return the form to the site study physician/coordinator after completing of all 
time points and prior to discharge from the hospital. The site study physician/coordinator will enter 
the data into REDcap forms: Baseline Observation Tool (Start of Study Treatment), 8-hour 
Observation Tool, 16-hour Observation Tool, 24-hour Observation Tool Follow the instructions 
above to enter these data into REDCap.  


 
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On the day of hospital discharge, call the 24h-monitored phone number at UC Davis (510-761-5406) and 
leave a message with the following information so that team can schedule the monitoring emails to be sent 
to the family starting the day after discharge.   
 
When you call, please provide:  
1. Subject study ID 
2. Date of the call 
3. Parent’s preferred email  
4. Your name  
5. Your contact information  
  
If the parent chooses paper, please collect the paper questionnaire at the follow-up visit.  Then scan and 
email the completed questionnaire to Samantha Roberts at sroberts@ucsd.edu. 
 
Compensation for Participation 
On completion of the parent observation daily observations, subjects will be provided with a $25 gift card 
at the follow-up visit to offset any incidental expenses for participation. The gift cards will be supplied by 
the UC Davis team to all sites at study initiation. Requests for additional cards should be made to calling 
Samantha Roberts at 858-966-8799 or email sroberts@ucsd.edu. 
How to complete the Parent Observation Tool Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.   Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section. 
          
 
10)  Click the subject ID that needs to be completed.   
 


 
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11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the 24h post 
completion of tx column and next to the Baseline, 8, 16, 24h Observation Tool for you need to 
complete    
 
          
 
    
12) When you click on the circle you will be taken to the Baseline, 8, 16, 24h Observation Tool form 
(Appendix B). 
13) Answer all the questions within the Baseline, 8, 16, 24h Observation Tool forms.  


 
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14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record 
 
 
 
 
15) From here you will be directed back to the subjects study dashboard. The circles next to the 
Baseline, 8, 16, 24h Observation Tool forms should be GREEN 
 
If the subject crosses over to the other study treatment, repeat steps 1-10 for the 8, 16, 24h Observation 
Tool form located under the Crossover of study tx column.   
5P. Adverse Event Reporting From 
1. Risks associated with second IVIG treatment 
1) Infusion reaction: Usually occurs during the first 1-2 hours of the infusion and is characterized by a 
sudden rise in temperature accompanied by rigors, hypotension, and distress. Caution must be 
exercised not to confuse fever from KD with fever and systemic signs associated with an infusion 
reaction. Treatment for a reaction is to stop the infusion, administer acetaminophen (15 mg/kg) and 
diphenhydramine (1mg/kg), and resume the IVIG infusion at half the rate at which the reaction 
occurred. Once the infusion is tolerated, the rate can be increased per standard nursing protocols. 
There are no published data re: frequency of this reaction with the second IVIG infusion. The rate is 
10-15% for the first infusion. In our previous infliximab clinical trial, none of 22 subjects receiving 
a second IVIG infusion had a reaction. 
2) Pain and tenderness at the infusion site. IVIG extravasation (pH 4.0) from a leaking IV can cause a 
3rd degree burn. 
3) Headache (13%)(Stiehm 2013) 
4) Abdominal pain (<5%) 
5) Sterile meningitis (<1%)(Orbach, Katz et al. 2005) 
6) Hemolytic anemia due to titers of anti-A and anti-B blood groups in the IVIG preparation. This is 
an emerging problem among treated patients with A, B, or AB blood types (3% in our experience at 
RCHSD) (Berard, Whittemore et al. 2012) 


 
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2. Risks associated with infliximab treatment 
1) Reactivation of latent mycobacterial or fungal infection: History of known TB, histoplasmosis, or 
coccidiomycosis would exclude subject from participating in the trial. Theoretically, an 
unrecognized latent infection with these agents could be converted to an active infection, although 
this has not been reported following a single dose. 
2) Infusion reactions (<1% for 1st infusion) 
3. Adverse Events 
An adverse event is any untoward medical occurrence experienced by a subject. An event constitutes a 
disease, a set of related symptoms or signs, or a single symptom or sign. 
 
 Adverse Events (AE) will be recorded according to the date and time of first occurrence, severity, and their 
duration, as well as any treatment, prescribed. Following initiation of study treatment, all new or continuing 
adverse events that were not present at enrollment will be recorded. Any medical condition present at the 
initial visit, which remains unchanged or improves, will not be recorded as an adverse event at subsequent 
visits. However, worsening of a medical condition that was present at the initial visit will be considered a 
new adverse event and reported. Abnormal laboratory values, if felt by the investigator to be clinically 
significant, will also be recorded on the AE form and assessed in terms of severity and relationship to study 
drug. Laboratory values that are abnormal at study entry and that do not worsen will not be recorded on the 
AE form.  The Adverse Events Committee will adjudicate the adverse events and determine if the event 
was ‘Not Related’, ‘Possible Related” or “Probably Related” to the study treatment.  The members of the 
Adverse Events Committee are Jane Burns, Adriana Tremoulet, Jane Newburger, and Anne Rowley 
 
The following will NOT be considered adverse events as these are commonly associated with KD: 
Neutropenia at follow-up visit when patients typically develop lymphocytic predominance 
Periungual desquamation 
Thrombocytosis 
4. Serious Adverse Events 
An SAE is defined as any event which:  
1. Is fatal; or  
2. Is life-threatening (the patient was, in the view of the Principal Investigator, in immediate danger of 
death from the event as it occurred); or  
3. Requires hospital admission or prolongs hospitalization; or  
4. Is persistent or causing significant disability; or  
5. Required medical intervention, such as major surgery, to prevent a serious outcome; or  
6. Is associated with a  congenital anomaly 
7. The Clinical Site Principal Investigator considers it to be a serious adverse event.  
 
SAEs for this trial include but are not limited to, prolonged hospitalization due to study treatment 
crossover, anaphylaxis, arrhythmia, cardiac arrest, cardiogenic shock, death, hearing loss, myocardial 
infarction, renal failure, seizures, sepsis (confirmed), or serious infection requiring hospitalization.  
 
Reporting Unanticipated Problems involving risk to subjects or others (URPs)  
What to report. The following events meets the definition of a URP and should be reported to Samantha 
Roberts (sroberts@ucsd.edu) within 5 working days: 


 
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a) Any serious adverse event (SAE) (including injured, side effects, deaths or other problems) 
that in the opinion of the Principal Investigator was unanticipated, involved risk to subjects 
or others, and was at least possibly related to the research procedures.  
b) Any serious accidental or unintentional change in the IRB-approved protocol that alters the 
level of risk 
c) Any deviation from the protocol taken without prior IRB review to eliminate apparent 
immediate hazard to a research subject 
d) Any new information (e.g. publication, safety monitoring report, updated sponsor safety 
report), interim result or other finding that indicates an unexpected change to the risk/benefit 
ratio of the research 
e) Any breach in confidentiality that may involve risk to the subject or others 
f) Any complaint of a subject that indicated an unanticipated risk or that cannot be resolved by 
the Principal Investigator 
 
 
Problems/events that are unanticipated and serious should be reported to the Samantha Roberts 
(sroberts@ucsd.edu) within 5 working days only if in the opinion of the Principal Investigator they are 
possibly, probably or definitely related to the research procedures. Those serious, unanticipated 
problems/events that the Principal Investigator deems unlikely or not related do NOT meet the IRB’s 
definition of UPRs; however, these events must be reported to the IRB at least annually at the time of 7-


 
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year “re-submission” or Continuing Review submission. Please report these events in the Adverse Event 
Form.  
 
Serious Adverse Events (SAEs) need to be entered into REDCap within 5 days of occurrence.  PCORI 
requires us to report all SAEs within 10 working days.  
Hemolytic Anemia  
This is a serious adverse event that can happen to subjects who are randomized to receive a second dose of 
IVIG.  Subjects with A ,B, or AB blood types are at higher risk to get hemolytic anemia.  If a subject is 
diagnosed with hemolytic anemia, please complete the Adverse Event Reporting form as well as the 
Hemolytic Anemia AE form.  The hemolytic anemia form includes some additional information that is 
collected once a patient is diagnosed with hemolytic anemia.  Not all of the requested information is 
required, but strongly suggested as a work up of hemolytic anemia in patients with KD.  Please include 
whatever information is standard of care at your institution for the work up of hemolytic anemia.   
 
Here is a list of the information we are requesting: 
 Blood Type 
 Creatinine 
 Total and direct bilirubin 
 Plasma hemoglobin 
 Urine hemoglobin 
 Haptoglobin 
 CBC with reticulocyte count 
 Direct and indirect antiglobulin test 
 Blood smear 
How to complete the Adverse Event Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  


 
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9) Click on the Record Status Dashboard under this section.           
 
 
 
10)  Click the subject ID that needs to be completed.   
 
           
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the Other Data 
column and next to the Adverse Event form you need to complete.  If applicable you can also 
complete the Hemolytic Anemia AE form, which is below the Adverse Event form.  
             
 
            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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12) When you click on the circle you will be taken to the Adverse Event form 
13) Answer all the questions within the Adverse Event form: 
 
      
 
 
 
       
If you have more than 1 
adverse event, answer 
yes to this question.  All 
the question will appear 
again for an additional 
entry. 


 
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If applicable complete the Hemolytic Anemia AE Form: 
 
 
 


 
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14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record 
 
 
 
 
15) From here you will be directed back to the subjects study dashboard. The circle next to the Adverse 
Event form should be GREEN. If you completed the Hemolytic Anemia AE form, that should also 
be GREEN.  
5Q. Protocol Deviations Form 
The following are examples of protocol deviations that need to be reported: 
1) Temperature route if measurement is not oral, rectal, or axillary 
2) Temperature is not taken at study enrollment or is taken outside the window of 24 (± 2) hours of 
study treatment initiation or study treatment completion. 
3) Laboratory measurements not completed within 24 ( ± 2) hours after completion of study treatment 
4) Laboratory measurements not completed within 5-18 days after completion of study treatment 
5) Echocardiogram measurement not completed within 5-18 days after completion of study treatment 
6) Follow-Up Visit not completed within 5-18 days after completion of study treatment 
 
If you have a protocol deviation, please complete the protocol deviation from on iDASH REDCap 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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How to complete the Protocol Deviations Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal you will see a section labeled Data Collection  
9) Click on the Record Status Dashboard under this section. 
           
 
 
10) Click the subject ID that needs to be completed.   
 
          
 
 
 
 


 
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11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the column and 
next to the Protocol Deviation form you need to complete. You can complete this Protocol 
Deviation form at any time point.  Enter the adverse event into to the time point it happened closest 
to.   
 
               
12) When you click on the circle you will be taken to the Protocol Deviation form 
 
 
 


 
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13) Answer all the questions within the Protocol Deviation form 
14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record 
 
 
 
 
15) From here you will be directed back to the subject’s study dashboard. The circle next to the 
Protocol Deviation form should be GREEN 
 
5R. Study Completion From 
Completed this form at the follow-up study Visit 
How to complete the Study Completion Form in REDCap: 
1) Go to https://cwp.ucsd.edu  
2) You will log in using your AD account username and password 
3) You should receive a login request on your phone from the Duo Mobile App 
4) Open the Duo Mobile App on your phone and approve the login request 
5) Once you have approved the login request, your browser will be directed to the Clinical Web Portal 
(CWP) 
6) Select the KD REDCap icon 
7) The REDCap database will be opened up in another web page.  Under My Projects, Choose 
KIDCARE Trial 2017 
8)  On the left side of the REDCap portal, you will see a section labeled Data Collection  
 
 
 
 
 
 
 
 
 
 


 
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9) Click on the Record Status Dashboard under this section. 
            
 
 
10) Click the subject ID that needs to be completed.   
 
          
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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11) You will then be taken to this subjects REDCap study dashboard.  This lists the time points and the 
forms that can be completed at each time point. You will click on the circle under the Follow-Up 
Visit column and next to the Study Completion form you need to complete.  
         
            
 
 
 
12) When you click on the circle you will be taken to the Study Completion form 
 
 
 
13) Answer all the questions within the Study Completion form  
 
 
 
 
 
 
 


 
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14) Once you complete this form, change the status of the form Incomplete to Complete and then click 
Save Record 
 
 
 
 
 
15) From here you will be directed back to the subject’s study dashboard. The circle next to the Study 
Completion form should be GREEN 
6. Additional Therapy 
6A. Crossover treatment  
Subjects with a fever (T ≥38°C orally or rectally or ≥37.5°C axillary/ T ≥100.4°F orally or rectally or ≥ 
99.5°F axillary) at 24 hours after completion of 1st study treatment will cross-over to receive the other study 
treatment.  You will need to document this in REDCap. This is also considered a Serious Adverse Event 
(SAE), since this additional treatment will prolong the hospitalization of the subject.  You will need to 
complete the following forms: 
 
1) Crossover Drug Administration Form 
2) Crossover Temperature Form 
3) Crossover Laboratory Results Form 
4) 8, 16, 24hr Observation Tool 
5) Adverse Event Reporting form 
  
6B. Management of Treatment-resistant Subjects 
Treatment-resistance will be defined as persistent or recrudescent fever (T ≥38°C orally or rectally or 
≥37.5°C axillary/ T ≥100.4°F orally or rectally or ≥ 99.5°F axillary) ≥ 24 hours and <7 days following 
completion of infusion of the 2nd (crossover) study treatment. Subjects who meet criteria for treatment-
resistance will be treated at the Center PI’s discretion. Treatments will be recorded on the Concomitant 
Medication Form. 


 
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6C. Additional Therapy for Coronary Artery Abnormalities  
Additional therapy for coronary artery abnormalities will be at the Center PI’s discretion. If possible, 
additional anti-inflammatory therapies (steroids, cyclosporine, cyclophosphamide) should be avoided. 
However, if clinically indicated in the opinion of the Center PI, the subject should remain on study and all 
ancillary treatment should be recorded on the Con Med CRF. Cardiac medications (B-blockers, enoxaparin, 
dobutamine, etc.) are administered at the discretion of the Center PI and recorded on the Con Med CRF. 
6D. Allowable concomitant medications 
The following medications may be given after patient enrollment into the study: 
1) Acetominophen: may be administered for documented fever but should NOT be given to treat pain 
(e.g. headache, joint pain) during hospitalization. If administered at home while on study, parent 
should be queried about medication usage and this should be documented at the follow-up visit. 
2) Naproxen: may be administered for arthralgia/arthritis, suggested dose of 15 mg/kg/day divided 
q12h for 5 days; suspend aspirin therapy while on naproxen. This therapy may mask fever and 
should only be used when clearly clinically indicated. 
3) Opioids: may be administered for pain 
This information will be entered into REDCap at the following time points (Appendix C):   
1) Enrollment 
2) 24 hours post imitation of study treatment 
3) 24 hours post completion of study treatment 
4) Follow-up study visit 
5) Any other time from enrollment to the follow-up study visit 
 
The following medications should NOT be administered to patients while on study: 
1) Ibuprofen while taking ASA 
7. Privacy and Confidentiality of Data 
Study personnel at each site will log on to the private study portal on the REDCap web page with 
individual user names and passwords to securely perform study data entry and edits.  
1. Data Access: Access to research data collected in this trial will be restricted to study team members 
at each site and UCSD study personnel. REDCap features include individualized user roles and 
privileges, password and user authentication security, SSL encryption, comprehensive auditing to 
record and monitor access and data changes, and electronic signatures (http://www.project-
redcap.org/software.php).   
2. Server Security: The database will be stored on a secure electronic server with user name and 
password log on for individual users and will be backed up nightly. The REDCap servers are virtual 
machines (VMs) located on secure UCSD CTRI space.  
Data privacy: Sensitive and protected health information (PHI) will not be collected as part of this clinical 
trial.  The trial investigators are committed to uphold the highest ethical standard in addition to 
internationally recognized standards of privacy protection for ensuring responsible patient data use. 
Computer and database security:  Access to data and applications can be defined on a per user basis.  Direct 


 
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database access is strictly controlled.  User access to each data set/table must be explicitly granted.  Every 
transaction performed on the database is logged with a timestamp and user information to establish an audit 
log, as outlined by FDA guidelines (CFR 21, Part 11). 
8. Statistical Considerations 
8A. Power and Sample Size Justification 
The study is sufficiently powered for a superiority clinical trial. For the primary endpoint, if we assume 53 
evaluable subjects per group (total N=106) in this 2-arm trial, we will have 80% power to detect a 
difference between the group proportions of 0.155.  We assume that the reference group proportion (i.e. 
2nd IVIG arm is 67%, i.e. 8 of 12 patients responding will be similar to our published clinical trial (Burns, 
Best et al. 2008). The infliximab arm proportion is assumed to be 89% (based on published clinical trial, 
i.e. 11 of 12 patients responding). The power was computed for the case in which the actual infliximab 
arm proportion is lower at 82.5%.  Statistical power is based on a two-sided, two sample binomial test for 
proportions, and a two-sided alpha=0.05 was used. Subjects will be in the study for two weeks following 
administration of study drug and there is a possibility that subjects could be lost to follow-up. Assuming 
5% attrition, we will need to enroll 112 subjects to get 106 evaluable patients.  
8B. Statistical Analysis Plan 
This section briefly describes the planned statistical analysis. The Statistical Analysis Plan (SAP) provides 
details. In case the language in this section differs from the language in the SAP, the SAP takes precedence.  
The SAP will be finalized prior to the study’s database lock.   
 
Since this is a superiority study design, an intent-to-treat (ITT) analysis will be used to analyze the outcome 
data regarding patient outcomes. Results will be reported as point estimates (odds ratios or mean 
differences across groups, as appropriate) and interval estimates (95% confidence intervals).  All tests of 
significance for the secondary outcomes will be 2-sided and Hochberg adjustments will be made for 
multiple comparisons.  A p-value ≤ 0.05 will be considered statistically significant.  Statistical analysis will 
be conducted using the statistical software R 3.3.2. (www.rproject.org).  Demographic and baseline 
characteristics will be compared between the study arms using Fisher’s exact test for categorical variables, 
and a two-sample t-test for continuous variables.  Appropriate non-parametric alternatives will be 
considered, if parametric assumptions fail.  There will be no planned interim analyses for efficacy or 
futility conducted for this study, but the Data and Safety Monitoring Board (DSMB) may modify this 
during ongoing safety monitoring. 
 
Analysis of Primary Outcome:  
The primary outcome (Specific Aim 1) of the study is cessation of fever within the specified time frame, 
which is a dichotomous (binary) variable.  Comparison between the infliximab and second IVIG arms will 
be compared using a Fisher’s exact test for proportions. Differences in the rates between the two groups, 
along with the odds ratio (OR) and their 95% confidence intervals will be reported.  As a 
secondary/sensitivity analysis, multivariable logistic regression analysis will be performed to study the 
association between clinical and demographic factors (age < 1 yr., sex, ESR, WBC, ANC, CRP) and 
intervention arm, adjusting for baseline demographic, stratification variables, and clinical characteristics. 
Variables significantly associated with both treatment group and outcome (p<0.10) will be included in a 
multivariable logistic regression model as covariates.  
 
 


 
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Analysis of Secondary Outcomes:   
The first secondary outcome will test the hypothesis that infliximab treatment will result in more rapid 
resolution of inflammation compared to second IVIG as measured by WBC, ANC, and levels of CRP at 24 
hours and 5-18 days following completion of study treatment. We cannot make power estimates for this 
secondary aim as there are no prior data to guide assumptions. Comparisons between the Infliximab and 
second IVIG arms will be compared using a two-sample, two-sided t-test at each time point separately. 
Point estimates and their 95% confidence intervals will be reported.  As a secondary/sensitivity 
analysis, multiple linear regression at each time point will be performed to study the association between 
clinical and demographic factors (age < 1 yr., sex, ESR, WBC, and ANC) and intervention arm, adjusting 
for baseline demographic, stratification variables, and clinical characteristics, including baseline CRP. 
Variables significantly associated with both treatment group and outcome (p<0.10) will be included in a 
multiple regression model as covariates. Appropriate non-parametric alternatives will be considered, if 
parametric assumptions fail. A mixed model repeated measures (MMRM) model with three repeated 
measures (baseline, 24 hours, and at 5-18 days following completion of study treatment) will evaluate 
changes between the study arms for the major dependent variables, i.e. WBC, ANC, and CRP. Participants 
will only be included in the MMRM model if they have both a baseline and at least one post-baseline 
measurement. The model will include as the dependent variable the change from baseline in the 
inflammation variable at each post-baseline visit for each dependent inflammation marker separately.  
Independent variables in the MMRM model will include treatment arm, visit, treatment arm-by-visit 
interaction, the inflammation variable at baseline and other covariates. Visits will be treated as a categorical 
variable. Unstructured variance-covariance structure will be used. 
 
Analysis of Secondary Outcomes:  
This secondary outcome (Specific Aim 3) will test the hypothesis that infliximab treatment will result in a 
change in coronary artery Zworst score of ≥ 0.5 standard deviation units as compared to second IVIG at 5-
18 days following completion of study treatment measured by echocardiography. We cannot make power 
estimates for this secondary aim as this there are no prior data to guide assumptions.  Methods analogous to 
the analysis of Specific Aim 2 will be applied, including t-tests and regression models. There is a concern 
about inter-rater reliability of different readers for the echocardiograms at the 25 sites. Inter-rater reliability 
analysis will be conducted using Cohen’s Kappa statistics and multi-level modeling to measure agreement.  
In addition, to minimize disagreement, the Coordinating Center has developed manuals used in previous 
clinical trials to help standardize performance of echocardiograms and the measurement of the coronary 
arteries. During the run in period, a de-identified echocardiogram on a KD patient will be submitted to the 
coordinating center at UCSD and the quality will be assessed and feedback given to the center PI. 
 
Analysis of Parent Observation Tool:  
We have already engaged the advisory board in development of this aim beginning with the pSCANNER 
grant in 2015.  Within the first two months of this project, we will conduct in-depth, semi-structured 
interviews of 6 parents who have recently had a child treated with IVIG and treated with infliximab to 
further understand the experience of the different treatments and confirm PROs of relevance to 
patients/parents. Qualitative analysis will be performed using a grounded theory approach to inductively 
develop themes (Charmaz 2006, Corbin and Strauss 2014). The research team and advisory board will 
create questions that represent the categories of themes. The questionnaire will then be pre-tested with 6 
KD parents with children recently treated for KD at UC San Diego or UC Davis  for logic and clarity using 
cognitive interviewing by phone (Beatty and Willis 2007). The questionnaire will be implemented with 
parents whose children are enrolled in the trial in order to compare the PROs and experience of treatment.  
The questionnaire responses will be numerically tabulated overall and by study arm. The results of the 
analysis will be summarized descriptively (point estimates and confidence intervals). The amount of 


 
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missing data will also be evaluated and compared between study arms. Comparisons by study arm will be 
evaluated by a two-sample t-test if parametric assumptions hold.  If the assumptions are violated, we will 
compare treatment arms by the Wilcoxon rank sum test.  No adjustments for multiple comparisons will be 
made, since the questions will be determined a priori as the questions of interest that will determine 
parental preference to the treatment arms. In addition, multiple regression (Likert scaled items) and logistic 
regression (binary items) will be applied to assess the contribution of demographic factors, e.g. age of child 
and parent, and experiential factors, e.g. previous illnesses, on the ratings of items. Open-ended questions 
will be analyzed with thematic content analysis based on grounded theory as described above. 
 
8C. Evaluation of Safety Outcomes 
Demographic and disposition data, drug administration, medical history, prior and concomitant 
medications, adverse events (AEs), clinical laboratory measurements, vital signs, physical exam (PE) 
findings, and all other safety data will be listed by subject and time point. All subjects who receive any 
study medication (even if infusion is stopped prematurely) will be included in the safety analysis. All safety 
data, including AEs, serious adverse events (SAEs), vital sign data, PE findings, clinical laboratory test 
results, and concomitant medications, will be listed by subject. Adverse events will be summarized by 
method of collection type, frequency, severity, relationship to study drug, any change in study drug 
administration, and number of subjects per treatment. The severity of all AEs and all hematologic and 
biochemical toxicities will be rated according to a pre-specified rating system to be finalized at the first All-
Hands investigator meeting. Changes in PE and laboratory values that are expected will be excluded as 
AEs. For example, normocytic, normochromic anemia and peeling of the extremities are expected as the 
normal evolution of the disease process. However, hemolytic anemia (a potential risk for second IVIG arm) 
or upper respiratory tract infection (a potential risk for infliximab arm) would not be expected and would be 
classified as AEs. Frequency of treatment-emergent AEs and SAEs will be described by each treatment 
group and compared using Fisher Exact tests. These data will be included in monthly reports prepared for 
the study team and in the regular reporting to the DSMB. 
9. Data Safety Monitoring Board 
The clinical trial will utilize a DSMB to evaluate ongoing data from this randomized phase III trial. The 
board will be composed of a pediatric infectious disease specialist, a pharmacologist, a pediatric 
cardiologist and a biostatistician who are not investigators in this specific project and have no real or 
potential conflicts of interest with the clinical study.   
 
The DSMB will meet every six months (or more frequently, if desired by the committee) to review 
enrollment and safety data.  The proposed study will not have any planned interim analyses for efficacy or 
futility. The safety review will be prepared by the biostatistician, Dr. Sonia Jain.  An open review will 
include demographics and trial summary for the total population.  The committee, statistician, Project 
Manager, and the PI will attend the open portion.  During the closed review, the PI and other study 
personnel will not see the data reported by study arm. The committee will review safety data by arm.  A 
formal recommendation by the DSMB committee will be given to the PI, which will be reported to the 
participating sites, UCSD HRPP, and PCORI as appropriate. 
 
 


 
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Appendix A: List of study sites and site investigators (from west to east) 
 
Site No. 
Collaborating Organization 
PI 
01 
University of California San Diego/Rady Children's Hospital 
Jane Burns 
Adriana Tremoulet 
03 
Children's Hospital of Orange County 
Negar Ashouri 
04 
Miller Children's Hospital, Long Beach 
David Michalik 
05 
Harbor-UCLA Medical Center 
Sylvia Yeh 
06 
Children's Hospital Los Angeles, Division of Cardiology 
Jackie Szmuszkovicz 
07 
David Geffen School of Medicine at UCLA 
Yvonne Bryson 
08 
Cedars-Sinai Medical Center 
Moshe Arditi 
09 
Stanford School of Medicine 
Cornelia Dekker 
10 
UCSF Benioff Children's Hospital-Oakland 
Gregory Kurio 
11 
UCSF Benioff Children's Hospital-San Francisco 
Amy McNelis 
12 
UC Davis Children's Hospital 
Katherine Kim 
13 
Seattle Children's 
Michael Portman 
14 
University of Utah Health Care 
Dongngan Truong 
15 
Children's Hospital Colorado 
Pei-Ni Jone 
16 
Texas Children's Hospital 
S. Kristen Sexson Tejtel 
17 
Children's Health, University of Texas Southwestern Medical Center 
Kavita Sharma, M.D. 
18 
University of South Dakota, Sanford School of Medicine 
Archana Chatterjee 
19 
Children's Mercy, Kansas City 
Mary Anne Jackson 
20 
Arkansas Children's Hospital 
Jose Romero 
21 
Batson Children’s Hospital 
Rana El Feghaly 


 
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22 
The Ann & Robert H. Lurie Children’s Hospital of Chicago 
Anne Rowley 
23 
The University of Chicago Department of Pediatrics 
Robert Daum 
24 
Vanderbilt School of Medicine 
Natasha Halasa 
25 
Emory University School of Medicine 
David Lloyd 
26 
Nationwide Children's Hospital 
Guliz Erdem 
27 
Children's National Health System 
Roberta DeBiasi 
29 
Maria Fareri Children's Hospital at Westchester Medical Center 
Supriya Jain, M.D. 
30 
Children's Hospital Boston 
Jane Newburger 
31 
Riley Children’s Hospital 
John Manaloor 
32 
University of Nebraska Medical Center 
Kari Simonsen 
33 
Children’s Hospital of Michigan 
Jocelyn Ang 
34 
Children’s Hospital of Pittsburgh of UPMC 
Margalit Rosenkranz 
35 
The University of Alabama at Birmingham 
Nichole Samuy 
 


 
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Appendix B: Parent observation tool 
 
Study ID _____________________ 
Date ____________ 
(To be filled in by study doctor) 
 
Please use this form to record observations about your child during treatment.  We ask that 
you record these observations at four times during the first 24-hour period that your child is 
in the study: 
5. Start of study treatment 
6. 8 hours after start of treatment 
7. 16 hours after start of treatment 
8. 24 hours after start of treatment. 
 
If your child receives an additional study treatment, we ask that you also record for the 
second 24-hours. 
4. 8 hours after start of second treatment 
5. 16 hours after start of second treatment 
6. 24 hours after start of second treatment. 
 
Before you leave the hospital return this form to ___________________________ (your 
study doctor). 


 
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Study ID ________________     Date ____________ Time recorded ___________ am/pm 
A. Start of study treatment. 
At any time from end of first IVIG until start of the current treatment did 
your child show any of the following signs or symptoms? 
Check 
     
Yes or  No 
1 Does your child seem like his/her usual self? 
 
 
2 Rash  
 
 
3 Red/bloodshot eyes 
 
 
4 Eyes are sensitive to light 
 
 
5 Swelling in hands 
 
 
6 Redness on hands/fingers 
 
 
7 Swelling in feet 
 
 
8 Redness on feet/toes  
 
 
9 Peeling on hands/fingers 
 
 
10 Peeling on feet/toes  
 
 
11 Headache 
 
 
12 Muscle/Joint Pain 
 
 
13 Difficulty eating or drinking 
 
 
14 Unwilling to smile  
 
 
15 Irritability 
 
 
16 Lack of interest in playing 
 
 
17 Lack of interest in physical activity 
 
 
18 Lack of interest in interacting with others 
 
 
19 Difficulty falling or staying asleep 
 
 
20 Describe any other issues you notice such as pain, discomfort, or unusual behaviors 
that appeared during this period.  Any other comments? 
 
 
 
 
 
 
 


 
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Study ID _________________  Date ____________ Time recorded ___________ am/pm 
B. 8 hours after start of study treatment. 
 
At any time from start of the study treatment did your child show any of the 
following signs or symptoms? 
Check 
     
Yes or  No 
1 Does your child seem like his/her usual self? 
 
 
2 Rash  
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
3 Red/bloodshot eyes 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
4 Eyes are sensitive to light 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
5 Swelling in hands 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
6 Redness on hands/fingers 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
7 Swelling in feet 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
8 Redness on feet/toes  
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
9 Peeling on hands/fingers 
 
 
10 Peeling on feet/toes  
 
 
11 Headache 
 
 
12 Muscle/Joint Pain 
 
 
13 Difficulty eating or drinking 
 
 
14 Unwilling to smile  
 
 
15 Irritability 
 
 
16 Lack of interest in playing 
 
 
17 Lack of interest in physical activity 
 
 
18 Lack of interest in interacting with others 
 
 
19 Difficulty falling or staying asleep 
 
 
20 Describe any other issues you notice such as pain, discomfort, or unusual behaviors that 
appeared during this period.  Any other comments? 
 
 
 


 
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Study ID _________________  Date ____________ Time recorded ___________ am/pm 
C. 16 hours after start of study treatment. 
 
At any time within 8 to 16 hours since the start of the study treatment did 
your child show the following signs or symptoms? 
Check 
     
Yes or  No 
1 Does your child seem like his/her usual self? 
 
 
2 Rash  
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
3 Red/bloodshot eyes 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
4 Eyes are sensitive to light 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
5 Swelling in hands 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
6 Redness on hands/fingers 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
7 Swelling in feet 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
8 Redness on feet/toes  
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
9 Peeling on hands/fingers 
10 Peeling on feet/toes  
 
 
11 Headache 
12 Muscle/Joint Pain 
 
 
13 Difficulty eating or drinking 
14 Unwilling to smile  
 
 
15 Irritability 
16 Lack of interest in playing 
 
 
17 Lack of interest in physical activity 
 
 
18 Lack of interest in interacting with others 
 
 
19 Difficulty falling or staying asleep 
 
 
20 Describe any other issues you notice such as pain, discomfort, or unusual 
behaviors that appeared during this period.  Any other comments? 
 
 
 Study ID _________________ Date ____________ Time recorded ___________ am/pm 


 
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D. 24 hours after start of study treatment. 
At any time within 16 to 24 hours since the start of the study treatment did 
your child show the following signs or symptoms? 
Check 
     
Yes or  No 
1 Does your child seem like his/her usual self? 
 
 
2 Rash  
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
3 Red/bloodshot eyes 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
4 Eyes are sensitive to light 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
5 Swelling in hands 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
6 Redness on hands/fingers 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
7 Swelling in feet 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
8 Redness on feet/toes  
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
 
 
9 Peeling on hands/fingers 
10 Peeling on feet/toes  
 
 
11 Headache 
12 Muscle/Joint Pain 
 
 
13 Difficulty eating or drinking 
14 Unwilling to smile  
 
 
15 Irritability 
16 Lack of interest in playing 
 
 
17 Lack of interest in physical activity 
 
 
18 Lack of interest in interacting with others 
 
 
19 Difficulty falling or staying asleep 
 
 
20 Describe any other issues you notice such as pain, discomfort, or unusual 
behaviors that appeared during this period.  Any other comments? 
 
 
 
 
 
 
 


 
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Day __: Study ID _______________  Date ____________ Time recorded _______ am/pm 
At any time in the last 24 hours did your child show the following 
symptoms? 
Check 
       
Yes or  No 
1 Fever (temperature above 38 C or 100.4 F) 
How was temperature measured? □ Oral    □ Rectal    □ Axillary (Armpit) 
  
  
2 Does your child seem like his/her usual self? 
  
  
3 Rash  
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
  
  
4 Red/bloodshot eyes 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
  
  
5 Eyes are sensitive to light 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
  
  
6 Swelling in hands 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
  
  
7 Redness on hands/fingers 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
  
  
8 Swelling in feet 
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
  
  
9 Redness on feet/toes  
If Yes:  Compared to 8 hours ago it is    □ Better     □ Same     □ Worse 
  
  
10 Peeling on hands/fingers 
  
  
11 Peeling on feet/toes  
  
  
12 Headache 
  
  
13 Muscle/Joint Pain 
  
  
14 Difficulty eating or drinking 
  
  
15 Unwilling to smile  
  
  
16 Irritability 
  
  
17 Lack of interest in playing 
  
  
18 Lack of interest in physical activity 
  
  
19 Lack of interest in interacting with others 
  
  
20 Difficulty falling or staying asleep 
  
  
21 Cold symptoms (runny nose, cough, sore throat) 
  
  
22 Vomiting 
  
  
23 Diarrhea 
  
  
24 Any other illnesses 
  
  


 
84 
10/14/2019 
 
 
 
Appendix C: Case Report Forms 
 
ELIGIBILITY EVALUATION  
 
Inclusion Criteria 
Yes 
No 
1. Is the patient at least 4 weeks to < 18 years old?  
 
 
 
2. Did patient have fever by parental history for 3 to 10 days prior to initial 
IVIG treatment? 
 
 
 
3. Does the patient meet AHA criteria for KD by one of the following? 
Please check one : 
  Four of five clinical KD criteria (Table 1) 
 
  At least 2 clinical criteria with left anterior descending /right coronary 
artery z-score ≥ 2.5 
 
  At least 2 clinical criteria with CRP ≥ 3 mg/dL or ESR ≥ 40 mm/hr 
and at least 3 supplemental laboratory criteria (Table 2) 
 
 
 
4. Does patient have fever (T ≥38°C orally or rectally or 37.5°C axillary) 
between 36 hours and 7 days after end of the first IVIG infusion without 
other likely cause? 
 
 
 
5. Is patient sexually active?                                    
 Not applicable 
 
 
 
6. If patient is sexually active is he/she willing to use contraception? 
                                                                                  
 Not applicable 
 
 
7. Is patient, or legal representative, capable and willing to give written 
informed consent?  
 
Date of Informed Consent:   _ _/ _ _/ _ _ _ _          (mm/dd/year) 
Time of Informed Consent:  _________________ (24-hr clock) 
 
                                                                             
 Not applicable 
 
 
 
Table 1. Diagnostic criteria for KD (Adapted from American Heart Association (McCrindle et al., 
Circulation, 2017)): 
KD standard clinical criteria : 
 
Erythema and cracking of lips, strawberry tongue, and/or erythema of oral and pharyngeal mucosa 
 
Bilateral bulbar conjunctival injection without exudate 
 
Rash: maculopapular, diffuse erythroderma, or erythema multiforme-like 
 
Erythema and edema of the hands and feet in acute phase and/or periungual desquamation in 
subacute phase 
 
Cervical lymphadenopathy (≥1.5 cm diameter), usually unilateral 


 
85 
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86 
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In order to qualify for the study, the following inclusion criteria must be met: 
 
Inclusion criteria questions 1-2, 4, and 7 must be marked "yes". 
 
Inclusion criteria question 3, one of the choices must be chosen.  
 
If Inclusion criteria question 5 is "no" or "not applicable" then patient is 
eligible.  
 
If Inclusion criteria question 5 is "yes" then question 6 needs to also be "yes" 
for the patient to be eligible.  
 
In order to qualify for the study, exclusion criteria questions 1-6 must be 
marked "no" 
 
Does the patient qualify for the study?    
 YES 
 NO 
 
 
Exclusion Criteria 
Yes 
No 
1. Has the patient been treated with infliximab or steroids for present illness 
(e.g. RAISE protocol)?  
a. Patients who received oral steroids as outpatients prior to KD 
diagnosis (e.g. for suspected allergic reaction) but who otherwise 
qualify for the study are not excluded 
 
 
 
2. Does the patient have any chronic disease, except asthma, atopic 
dermatitis, autism or controlled seizure disorder?  
 
 
 
3. Does the patient have a known prior infection with tuberculosis, 
coccidiomycosis, or histoplasmosis? 
 
 
 
4. Has the patient used of a TNFα blocker within the 3 months prior to 
enrollment? 
 
 
 
5. Does the patient have a history of hypersensitivity to infliximab? 
 
 
 
6. Does the patient have a household member with active TB? 
 
 


 
87 
10/14/2019 
 
Trial Arms Form 
 
Is the patient eligible for study?  
 Yes 
 No 
 
Date of Randomization  
 
(MM-DD-YYYY) 
 
Site Number 
_______ (01-40) 
 
Sex: 
 Male 
 Female 
 
Age Group 
 Less than or equal to 12 months 
 Greater than 12 months 
 
 
Subject then randomized to receive either Infliximab (10mg/kg) or Second IVIG (2g/kg)  
 


 
88 
10/14/2019 
 
TEMPERATURE (1st Study Drug) 
Temperature recorded is the temperature-qualifying patient for study enrollment. Patient needs to 
have a fever T ≥38.0°C orally or rectally or T ≥37.5°C axillary/ T ≥100.4°F orally or rectally or ≥ 
99.5°F axillary 
 
 
Date 
(mm/dd/yyyy) 
Time 
(24 hour 
clock) 
Temperature  
(indicate 
Centigrade or 
Fahrenheit) 
Route 
 
 
 
 
Oral 
Rectal Axillary 
Other, 
Please 
Specify: 
 
Aspirin (before 
temp measured) 
 
 
N/A 
N/A 
N/A 
N/A 
N/A 
Temperature 
qualifying subject 
for study 
enrollment  
 
 
  
 
 
 
 
 
 


 
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STUDY DRUG ADMINISTRATION 
Subject weight ___________ kg 
Subject randomized to: 
  2nd IVIG 
 
  Infliximab 
 
Complete appropriate table below: 
2nd IVIG 
Start Date: 
                                                                (mm/dd/year) 
Start Time:  
                                                                 (24-hr clock)  
Stop Date: 
                                                                (mm/dd/year) 
Stop Time:   
                                                (24-hr clock) 
Total grams administered: 
*Dosing protocol: 2g/kg over 8-10hr 
                                                                     grams 
Brand: 
                                                                       
Lot # 
 
 
IVIG INFUSION REACTION:                            
 Yes 
 No 
 
 
If yes, complete AE form 
 
Infliximab 
Start Date: 
                                                                    (mm/dd/year) 
Start Time:  
                                                                 (24hr clock)  
Stop Date: 
                                                                (mm/dd/year) 
Stop Time:   
                                                (24-hr clock) 
Total milligrams administered: 
*Dosing protocol: 10mg/kg over a min 2hr 
mg  
Brand: 
 
 
INFLIXIMAB INFUSION REACTION:           
 Yes   
 No 
  If yes, complete AE form 
 


 
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TEMPERATURE (1st Study Drug) 
 
 
Date 
(mm/dd/yyyy) 
Time 
(24 hour 
clock) 
Temperature  
(indicate 
Centigrade or 
Fahrenheit) 
Route 
 
 
 
 
Oral 
Rectal Axillary 
Other, 
Please 
Specify: 
 
Aspirin (before 
temp measured) 
 
 
N/A 
N/A 
N/A 
N/A 
N/A 
24 hours(± 2h) 
from initiation of 
study treatment 
 
 
  
 
 
 
 
 
PRIMARY OUTCOME: 
Was subject afebrile (<38°C rectally or orally or 37.5°C axillary/ T <100.4°F orally or rectally 
or < 99.5°F axillary) 24h after initiation of study treatment:                             
 
 Yes 
 No
 
 
 
 


 
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TEMPERATURE (1st Study Drug) 
 
 
Date 
(mm/dd/yyyy) 
Time 
(24 hour 
clock) 
Temperature  
(indicate 
Centigrade or 
Fahrenheit) 
Route 
 
 
 
 
Oral 
Rectal Axillary 
Other, 
Please 
Specify: 
 
Aspirin (before 
temp measured) 
 
 
N/A 
N/A 
N/A 
N/A 
N/A 
24 hours (± 2h)  
from completion 
of study treatment 
 
 
 
  
 
 
 
 
 
 
SECONDARY OUTCOME: 
Was subject afebrile (<38°C rectally or orally or 37.5°C axillary /T <100.4°F orally or rectally 
or < 99.5°F axillary) 24h after completion of study treatment and remained afebrile until 
discharge:                             
 
 Yes 
 No
 
 
 
If no, then complete Crossover Temperature Measurement Form 
 


 
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10/14/2019 
 
LABORATORY RESULTS 
Please check one study visit: 
 
 Baseline (pre-IVIG)      
 24 hours (± 2 hrs) post completion of 1st study treatment      
 Follow up visit. 5-18 days post completion of study treatment     
 Other (Specify) _____________ 
 
  
 
 
Erythrocyte 
sedimentation rate 
(ESR) 
Date 
(mm/dd/yyyy) 
Time 
(24 hour 
clock) 
Value 
Comment 
ESR (mm/hr) 
 
 
 
 
***Should only be completed at enrollment and follow up visit 
**** If ESR > 140 write in '140' 
 
Chemistry 
Date 
(mm/dd/yyyy) 
Time 
(24 hour 
clock) 
Value 
Comment 
CRP (mg/dL) 
 
 
 
 
 
 
 
Hematology
 
 
Date 
(mm/dd/yyyy) 
Time 
(24 hour 
clock) 
Value 
Comment 
White Blood Cell Count (X103/uL) 
 
 
 
 
Hemoglobin (g/dL) 
 
 
 
 
Platelet Count (X103/uL) 
 
 
 
 
Neutrophils (%) 
 
 
 
 
Bands (%) 
 
 
 
 
Absolute Neutrophil Count (ANC) 
 
 
 
 


 
93 
10/14/2019 
 
Urine pregnancy test 
(female patients if applicable) 
 
 
 positive         
 negative 
 N/A 
 
***Prefer value given in mg/dL 
If CRP is below level of detection, write in the value of lower limit of detection of lab. e.g. if values are < 0.5 
mg/dL, write in '0.5' 
 
 
 
 
 


 
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CENTER ECHOCARDIOGRAM  
Please check one study visit: 
 
 Enrollment, Pre-IVIG (Echocardiogram at during initial hospitalization at the time of diagnosis.  As soon 
after admission as possible)        
 5-18 days after completion of study treatment    
 If coronary artery abnormalities, worst echo between enrollment and follow-up visit 
 
Date Study Done 
(mm/dd/year) 
                                                                                                              
Height (cm) 
 
Weight (kg) 
 
Coronary Artery 
Data: 
 
 
LMCA 
 
________(mm)                                    
 Not well seen 
 
Proximal LAD 
 
________(mm)                                    
 Not well seen 
 
Circumflex  
 
________(mm)                                    
 Not well seen 
 
Proximal RCA 
 
________(mm                                     
 Not well seen 
 
Mid RCA 
 
________(mm                                     
 Not well seen 
Comments 
 
 
 
 
 
 
 
 
 
 
 


 
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10/14/2019 
 
TEMPERATURE (Crossover) 
 
 
Date 
(mm/dd/yyyy) 
Time 
(24 hour 
clock) 
Temperature  
(indicate 
Centigrade or 
Fahrenheit) 
Route 
 
 
 
 
Oral 
Rectal Axillary 
Other, 
Please 
Specify: 
 
Aspirin (before 
temp measured) 
 
 
N/A 
N/A 
N/A 
N/A 
N/A 
Temperature 
qualifying subject 
for crossover 
 
 
 
 
 
 
 
Aspirin (before 
temp measured) 
 
 
N/A 
N/A 
N/A 
N/A 
N/A 
24 hours(± 2h) 
from initiation of 
study crossover 
treatment 
 
 
  
 
 
 
 
Aspirin (before 
temp measured) 
 
 
N/A 
N/A 
N/A 
N/A 
N/A 
24 hours (± 2h)  
from completion 
of study 
crossover 
treatment 
 
 
 
  
 
 
 
 
 
OUTCOME Questions: 
 
 
Was subject afebrile (<38°C rectally or orally or 37.5°C axillary/ T <100.4°F orally or rectally 
or <99.5°F axillary) 24h after initiation of study crossover treatment:                             
 
 Yes 
 No
 
 
 
Was subject afebrile 24h after completion of study crossover treatment and remained 
afebrile until discharge:                             
 
 Yes 
 No 


 
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10/14/2019 
 
CROSSOVER LABORATORY RESULTS 
 
 
 
 
Hematology
 
 
Date 
(mm/dd/yyyy) 
Time 
(24 hour 
clock) 
Value 
Comment 
White Blood Cell Count 
(X103/uL) 
 
 
 
 
Hemoglobin (g/dL) 
 
 
 
 
Platelet Count  (X103/uL) 
 
 
 
 
Neutrophils (%) 
 
 
 
 
Bands (%) 
 
 
 
 
Absolute Neutrophil Count 
(ANC) 
 
 
 
 
 
 
 
Chemistry 
Date 
(mm/dd/yyyy
) 
Time 
(24 hour 
clock) 
Value 
Comment 
CRP (mg/dL) 
 
 
 
 
***Prefer value given in mg/dL 
If CRP is below level of detection, write in the value of lower limit of detection of lab. e.g. if values are < 0.5 
mg/dL, write in '0.5' 
 
 
 


 
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CROSSOVER STUDY DRUG ADMINISTRATION 
Did subject have a fever (T ≥38°C orally or rectally or ≥37.5°C axillary/ T ≥100.4°F 
orally or rectally or ≥ 99.5°F axillary) at 24 hours after completion of 1st study 
treatment  
  Yes (if yes, then complete section below)   
  No 
 
Which of the following treatments did the subject crossover to: (check one and 
complete appropriate table below): 
  2nd IVIG 
 
 
  Infliximab 
2nd IVIG 
Start Date: 
                                                                (mm/dd/year) 
Start Time:  
                                                                 (24-hr clock)  
Stop Date: 
                                                                (mm/dd/year) 
Stop Time:   
                                                (24-hr clock) 
Total grams administered: 
*Dosing protocol: 2g/kg over 8-10hr 
                                                                     grams 
Brand: 
                                                                       
Lot # 
 
Comments: 
 
 
 
IVIG INFUSION REACTION:                            
 Yes 
 No
 
 
If yes, complete AE form 
 
Infliximab 
Start Date: 
                                                                    (mm/dd/year) 
Start Time:  
                                                                 (24hr clock)  
Stop Date: 
                                                                (mm/dd/year) 
Stop Time:   
                                                (24-hr clock) 
Total milligrams administered: 
*Dosing protocol: 10mg/kg over a min 2hr 
mg  
Comments: 
 
 
INFLIXIMAB INFUSION REACTION:                
 Yes       
 No   If yes, complete 
AE form 
 
 
 
 


 
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PROTOCOL DEVIATION REPORTING FORM  
 
 
Date of Occurrence ________________________ (mm/dd/year) 
 
1. Describe the protocol deviation: _____________________ 
______________________________________________________________________ 
______________________________________________________________________ 
 
2. Explain the reason for the protocol deviation: ___________ 
______________________________________________________________________ 
______________________________________________________________________ 
 
3. Was the subject adversely affected by the deviation? 
   No 
  Yes    
If “Yes”, please specify: ___________________________ 
           If Yes, complete an AE Form  
4. Describe action taken to prevent recurrence: ________________________________ 
______________________________________________________________________ 
______________________________________________________________________ 
 
 


 
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ADVERSE EVENT REPORTING FORM 
 
Adverse Event 
Description 
 
 
 
 
Date and Time of 
Onset  
 
_ _ /_ _/ _ _ _ _mm/dd/year   _ _ _ _ (24-hr clock) 
 
Outcome 
 
 Ongoing   
 Resolved, no residual effect  
 Resolved, residual effects 
 Unknown 
 
Resolution Date 
           
_ _/ _ _ / _ _ _ _mm/dd/year 
  Continuing    
 Unknown 
 
 
Frequency 
 
 Single                        
  Continuous                           
  Intermittent 
Action Taken 
(check all that 
apply) 
 No interruptions in study treatment    
 Modified dose/rate including temporary interruptions 
 Study drug/procedure discontinued        
 Medication provided (complete concomitant medication form)      
Other-please specify __________________________________________ 
 
Relationship to  
Study treatment? 
 Definitely related     (The AE is clearly related to the study treatment ) 
 Probably related      (The AE is likely related to the  study treatment ) 
 Possibly related       (The AE may be related to the study treatment ) 
 Probably NOT related (The AE is doubtfully related to the study treatment) 
 Not related 
Does the Event 
Meet Criteria for 
Serious?  
 
Yes                                  
 No 
If yes, please specify. Check all that apply. 
Fatal 
 Life-threatening 
  Prolong hospital admission 
  Severely or permanently disabling 
  Required intervention to Prevent Permanent Impairment Damage 
The principal investigator considers it to be a serious adverse event 
 Other-please specify________________________________________ 
For an SAE, has the event been reported to IRB? 
Yes                                  
 No 
Date:______________________ 
 
Is the Event 
Anticipated? 
Yes                                  
 No 
 
*** Problems/events that are unanticipated and serious should be reported to 
the Samantha Roberts (sroberts@ucsd.edu) within 5 working days 
Comments: 
 
 
 


 
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10/14/2019 
 
FEVER DAYS 
 
Total number of fever days (24 hour period with a T ≥38°C orally or rectally or 
≥37.5°C axillary/ T ≥100.4°F orally or rectally or ≥ 99.5°F axillary) from time of start 
of infusion of first study treatment: ___________ days 
 
***A day is from 12:01am to 12:00 midnight.  
 
Example: If patient starts first study treatment at 1:00 am and becomes afebrile at 
11:00 pm that night, then that is one fever day. If fever returns two days later at 
1:00 am and patient receives second study treatment and becomes afebrile at 
11:00pm that night, then this counts as another fever day.  The total fever days this 
patient will have had is 2. 
 
DURATION OF HOSPITALIZATION 
 
Duration of hospitalization following study entry (count number of days from 
randomization; each 24h-period from 12:01am to 12 midnight counts as one 
calendar day): _____________ days 
 


 
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CONCOMITANT MEDICATION 
 
Provide the trade or generic name and route for all medications taken during study-specific time period. 
Provide the medication stop date or check “Continues”. 
 
 
Medication: 
 
Dose, specify 
units (ug/mg/g) 
 
 
Dosage(mg/kg): 
 
  
 
Frequency: 
 
 
 
Route: 
 
 Oral             
 Topical 
 Subcutaneous 
 IV 
 Other  (Specify): _____________________________________ 
 
 
Start Date: 
 
_____________________                                                       
     mm / dd / year            
     
 
Start Time: 
 
__________________        
     (24-hr clock) 
 
 
Stop Date: 
 
__________________ 
    mm / dd / year            
 
 
Stop Time: 
 
__________________        
     (24-hr clock) 
 
Reason for 
Therapy 
(Diagnosis)  
 
_______________________________________________________________ 
_______________________________________________________________ 
 
 
 
 


 
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