Trial Outcomes & Findings for A Randomized, Double Blind, Placebo Controlled Study of Etanercept in Children With Kawasaki Disease (NCT NCT00841789)
NCT ID: NCT00841789
Last Updated: 2023-05-06
Results Overview
The primary outcome is the proportion of subjects who become refractory to IVIG. Subjects requiring 1 dose of IVIG are classified as responders and subjects requiring more than 1 dose are classified as IVIG refractory.
COMPLETED
PHASE2
205 participants
42 days after initial dose
2023-05-06
Participant Flow
Participant milestones
| Measure |
Arm 1 -Etanercept
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
Etanercept: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
Placebo
Placebo
Placebo: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
|---|---|---|
|
Overall Study
STARTED
|
103
|
102
|
|
Overall Study
COMPLETED
|
98
|
99
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Randomized, Double Blind, Placebo Controlled Study of Etanercept in Children With Kawasaki Disease
Baseline characteristics by cohort
| Measure |
Arm 1 -Etanercept
n=100 Participants
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
Etanercept: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
Arm-2 Placebo
n=101 Participants
Placebo
Placebo: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
Total
n=201 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
100 Participants
n=99 Participants
|
101 Participants
n=107 Participants
|
201 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
3.77 years
STANDARD_DEVIATION 2.67 • n=99 Participants
|
3.66 years
STANDARD_DEVIATION 2.75 • n=107 Participants
|
3.70 years
STANDARD_DEVIATION 2.71 • n=206 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=99 Participants
|
40 Participants
n=107 Participants
|
74 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
66 Participants
n=99 Participants
|
61 Participants
n=107 Participants
|
127 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
19 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
36 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
81 Participants
n=99 Participants
|
84 Participants
n=107 Participants
|
165 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
15 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
29 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
54 Participants
n=99 Participants
|
60 Participants
n=107 Participants
|
114 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
18 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
36 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Region of Enrollment
Canada
|
16 participants
n=99 Participants
|
16 participants
n=107 Participants
|
32 participants
n=206 Participants
|
|
Region of Enrollment
United States
|
84 participants
n=99 Participants
|
85 participants
n=107 Participants
|
169 participants
n=206 Participants
|
|
KD Patients treated with IVIG
|
100 Participants
n=99 Participants
|
101 Participants
n=107 Participants
|
201 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 42 days after initial dosePopulation: All patients receiving study drug
The primary outcome is the proportion of subjects who become refractory to IVIG. Subjects requiring 1 dose of IVIG are classified as responders and subjects requiring more than 1 dose are classified as IVIG refractory.
Outcome measures
| Measure |
Arm 1 -Etanercept
n=100 Participants
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
Etanercept: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
ARM 2 Placebo
n=101 Participants
Placebo
Placebo: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
|---|---|---|
|
IVIG Refractory
|
13 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: 42 days after initial dosePopulation: All patients receiving study drug with coronary measures improved
The primary echocardiographic outcome will be the proportion of subjects with improvement defined as (20% change in coronary artery) from the worst findings during the acute study period (scheduled visits from admission to visit 4, including any unscheduled visits) to the primary study outcome time-point at visit 5 (visit 5). This calculation will be based on changes in absolute values and not z-scores as initially planned. Groups will be compared using a logistic model including a binary term for age \< versus \> 1 year. Two aspects of the echo findings will be considered: * Maximum aneurysm size and * Maximum measurements for left main coronary artery (LMCA), left anterior descending artery (LAD) and right coronary artery (RCA). * Change in diameter of each coronary artery will be determined at standard measurement location or aneurysm with the latter taking precedent.
Outcome measures
| Measure |
Arm 1 -Etanercept
n=100 Participants
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
Etanercept: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
ARM 2 Placebo
n=101 Participants
Placebo
Placebo: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
|---|---|---|
|
Determine if Etanercept Treatment Alters the Rate of Coronary Artery Dilation and Disease (CAD) at 2 and 6 Weeks After Treatment in Patients With Dilated Coro
|
56 Participants
|
53 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 weeksPopulation: Includes patients categorized by baseline coronary artery dilation (echocardiography) with stable or improved coronary artery z score
Overall change in coronary z score over time determined using General Estimating Equation in patients from baseline within patients. No change or improved defined by 20% change in z score. A Z score normalized for body surface area represents how much larger (or smaller) a measured coronary artery internal diameter by echocardiography is compared to the average coronary artery diameter for a child of the same size (body surface area includes both height and weight). There is no minimum or maximum value. Z score above 2.0 is at least 2 standard deviations above mean for population and is considered abnormal. A decrease in z score is favorable.
Outcome measures
| Measure |
Arm 1 -Etanercept
n=98 Participants
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
Etanercept: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
ARM 2 Placebo
n=99 Participants
Placebo
Placebo: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
|---|---|---|
|
Change in Coronary Artery Dimension by z Score Compared With General Estimating Equation
|
-0.4 units on a scale
Standard Error .122
|
-0.10 units on a scale
Standard Error 0.159
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 weeksPopulation: KD patients with dilated coronary arteries at baseline (improved or stable)
Overall change in z score over time determined using General Estimating Equation in patients with dilated coronary artery at baseline within patients. Overall change in coronary z score over time determined using General Estimating Equation in patients from baseline within patients. A Z score normalized for body surface area represents how much larger (or smaller) a measured coronary artery internal diameter by echocardiography is compared to the average coronary artery diameter for a child of the same size (body surface area includes both height and weight). There is no minimum or maximum value. Z score above 2.0 is at least 2 standard deviations above mean for population and is considered abnormal. A decrease in z score is favorable.
Outcome measures
| Measure |
Arm 1 -Etanercept
n=24 Participants
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
Etanercept: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
ARM 2 Placebo
n=22 Participants
Placebo
Placebo: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
|---|---|---|
|
Overall Change in z Score Over Time in Patients With Dilated Coronary Artery at Baseline Within Patients.
|
-081 score on a scale
Standard Error 0.39
|
0.4 score on a scale
Standard Error 0.81
|
Adverse Events
Arm 1 -Etanercept
Arm -2 Placebo
Serious adverse events
| Measure |
Arm 1 -Etanercept
n=99 participants at risk
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
Etanercept: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
Arm -2 Placebo
n=102 participants at risk
Placebo
Placebo: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
|---|---|---|
|
Immune system disorders
Hospital readmission for retreatment
|
7.1%
7/99 • Number of events 7 • 42 days
Does not differ from clinicaltrials.gov
|
9.8%
10/102 • Number of events 10 • 42 days
Does not differ from clinicaltrials.gov
|
|
Infections and infestations
Infection
|
2.0%
2/99 • 42 days
Does not differ from clinicaltrials.gov
|
0.00%
0/102 • 42 days
Does not differ from clinicaltrials.gov
|
Other adverse events
| Measure |
Arm 1 -Etanercept
n=99 participants at risk
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
Etanercept: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
Arm -2 Placebo
n=102 participants at risk
Placebo
Placebo: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
10.1%
10/99 • Number of events 10 • 42 days
Does not differ from clinicaltrials.gov
|
11.8%
12/102 • Number of events 12 • 42 days
Does not differ from clinicaltrials.gov
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place