Trial Outcomes & Findings for KIDCARE (Kawasaki Disease Comparative Effectiveness Trial) (NCT NCT03065244)

NCT ID: NCT03065244

Last Updated: 2021-12-03

Results Overview

A fever will be considered ≥38°C rectally or orally and ≥ 37.5°C axillary. Cessation of fever within 24h of initiation of study treatment with no fever recurrence within next 7 days.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 105 participants
• Primary outcome timeframe: 7 days
• Results posted on: 2021-12-03

Participant Flow

Participant milestones

Measure	IVIG Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Overall Study STARTED	50	55
Overall Study Participants Who Failed 1st Treatment and Crossed Over to Receive Other Treatment	22	9
Overall Study COMPLETED	47	51
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Measure	IVIG Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Overall Study Lost to Follow-up	1	1
Overall Study Diagnosed with a different disease	1	1
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)

Baseline characteristics by cohort

Measure	IVIG n=49 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=54 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours	Total n=103 Participants Total of all reporting groups
Age, Continuous	2.1 years n=5 Participants	3.6 years n=7 Participants	2.9 years n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	25 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	17 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized White	31 Participants n=5 Participants	29 Participants n=7 Participants	60 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Multi-race	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
WBC(white blood cells count)	13.6 cells*10^9/L n=5 Participants	12.8 cells*10^9/L n=7 Participants	13.0 cells*10^9/L n=5 Participants
Z-Worst	1.3 Standard Deviation units n=5 Participants	1.1 Standard Deviation units n=7 Participants	1.3 Standard Deviation units n=5 Participants
Illness Day at first IVIG	6.0 days n=5 Participants	6.0 days n=7 Participants	6.0 days n=5 Participants
Incomplete KD	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
ANC (absolute neutrophil count	9384.0 cells n=5 Participants	8449.0 cells n=7 Participants	9062.0 cells n=5 Participants
zHgb	-2.3 g/dL n=5 Participants	-2.3 g/dL n=7 Participants	-2.3 g/dL n=5 Participants
PLT (platelet count)	359.5 cells*10^9/L n=5 Participants	342.0 cells*10^9/L n=7 Participants	349.0 cells*10^9/L n=5 Participants
ESR (erythrocyte sedimentation rate),	68.5 mm/h n=5 Participants	56.5 mm/h n=7 Participants	63.0 mm/h n=5 Participants
CRP (C-reactive protein)	9.0 mg/dL n=5 Participants	14.1 mg/dL n=7 Participants	12.0 mg/dL n=5 Participants

PRIMARY outcome

Timeframe: 7 days

A fever will be considered ≥38°C rectally or orally and ≥ 37.5°C axillary. Cessation of fever within 24h of initiation of study treatment with no fever recurrence within next 7 days.

Outcome measures

Measure	IVIG n=49 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=52 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Number of Participants With Cessation of Fever Within 24h of Initiation of Study Treatment With no Fever Recurrence Within Next 7 Days.	25 Participants	40 Participants

SECONDARY outcome

Timeframe: 24h

Change in white blood cell count (WBC), between baseline and 24 hours and 2 weeks following study treatment.

Outcome measures

Measure	IVIG n=48 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=52 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Change in White Blood Cell Count (WBC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. Change WBC (Baseline & 24 hr after study treatment completion)	-2.05 cells* 10^9/L Interval -6.03 to 2.85	0.15 cells* 10^9/L Interval -2.43 to 4.6
Change in White Blood Cell Count (WBC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. Change WBC (Baseline & Follow-up Visit )	-4.9 cells* 10^9/L Interval -9.7 to 13.4	-3.5 cells* 10^9/L Interval -7.7 to 1.25

SECONDARY outcome

Timeframe: 2 weeks

Zworst score is 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. A Z-score >= 2.5 is considered a aneurysm according to the American Heart Association criteria.

Outcome measures

Measure	IVIG n=45 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=45 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Change in Zworst Score Between Baseline and 2-week (± 4 Days) Echocardiograms	-0.31 Standard Deviation units Interval -0.81 to 0.06	-0.01 Standard Deviation units Interval -0.42 to 0.68

SECONDARY outcome

Timeframe: 7 days

Determine the number of days a participant had a fever once the participant has been enrolled into the study.

Outcome measures

Measure	IVIG n=48 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=52 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Total Number of Fever Days (24 Hour Period With a T≥38.0°C) From Enrollment	2 days Interval 1.0 to 3.3	1 days Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: 2 weeks

How long a participant was hospitalized for.

Outcome measures

Measure	IVIG n=48 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=25 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Duration of Hospitalization	4 days Interval 3.0 to 6.0	2.5 days Interval 2.0 to 4.0

SECONDARY outcome

Timeframe: 7 days

Determine any complications and/or reactions to each treatment.

Outcome measures

Measure	IVIG n=49 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=54 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Number of Participants With IVIG and Infliximab Infusion Reactions and Complications	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 24h

Change in absolute neutrophil count (ANC) between baseline and 24 hours and 2 weeks following study treatment.

Outcome measures

Measure	IVIG n=48 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=52 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Change in Absolute Neutrophil Count (ANC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. Change ANC (Baseline & 24 hr after study treatment completion	-3398.4 cells Interval -7598.45 to 2320.5	-1742 cells Interval -4406.4 to 507.0
Change in Absolute Neutrophil Count (ANC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. Change ANC(Baseline & Follow-up visit)	-5853.5 cells Interval -10669.6 to -3236.6	-4661.0 cells Interval -8799.3 to -2731.0

SECONDARY outcome

Timeframe: 24h

Change in C-reactive protein (CRP, mg/dL) concentration between baseline and 24 hours and 2 weeks following study treatment.

Outcome measures

Measure	IVIG n=48 Participants Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=52 Participants Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Change in C-reactive Protein (CRP, mg/dL) Concentration Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. Change CRP (Baseline & 24 hr after study treatment completion )	-4.6 mg/dL Interval -11.6 to -1.9	-4.7 mg/dL Interval -11.3 to -2.0
Change in C-reactive Protein (CRP, mg/dL) Concentration Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. Change CRP(Baseline & Follow-up visit)	-8.6 mg/dL Interval -15.9 to -4.7	-13.4 mg/dL Interval -19.5 to -5.4

Adverse Events

IVIG

Serious events: 27 serious events

Other events: 6 other events

Deaths: 0 deaths

Infliximab

Serious events: 10 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	IVIG n=49 participants at risk Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=54 participants at risk Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Blood and lymphatic system disorders Hemolytic Anemia	20.4% 10/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
General disorders Continued Fever after treatment completion and crossover to other study treatment	44.9% 22/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	16.7% 9/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
General disorders Fever following crossover treatment	6.1% 3/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	14.8% 8/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Immune system disorders Dress Syndrome	0.00% 0/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Gastrointestinal disorders Pancreatitis	0.00% 0/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.

Other adverse events

Measure	IVIG n=49 participants at risk Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours	Infliximab n=54 participants at risk Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
Gastrointestinal disorders GI Symptoms	8.2% 4/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	5.6% 3/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Skin and subcutaneous tissue disorders Rash	10.2% 5/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	3.7% 2/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Musculoskeletal and connective tissue disorders Arthritis/pain and swelling in extremities	8.2% 4/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	3.7% 2/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Blood and lymphatic system disorders Epistaxis	6.1% 3/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	3.7% 2/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
General disorders Fever after discharge not attributed to KD	6.1% 3/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	14.8% 8/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
General disorders Headache	4.1% 2/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Infections and infestations URI	4.1% 2/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Blood and lymphatic system disorders Leukemoid Reaction	0.00% 0/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
General disorders Chest Pain	0.00% 0/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
General disorders Hyperhidrosis	0.00% 0/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Skin and subcutaneous tissue disorders Pain (IV Site)	0.00% 0/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
Eye disorders Color Blindness	0.00% 0/49 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.	1.9% 1/54 • Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.

Additional Information

Dr. Jane Burns

Dept. of Pediatrics UCSD School of Medicine

Phone: 858-246-0155

Email: jcburns@health.ucsd.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place