Mucocutaneous Lymph Node SyndromePhase 2NCT00841789
A Randomized, Double Blind, Placebo Controlled Study of Etanercept in Children With Kawasaki Disease
A Phase 2 study testing Etanercept in people with Mucocutaneous Lymph Node Syndrome and Kawasaki Disease, run by Michael Portman at 8 sites in 2 countries.
Trial summary
The purpose of this study is to determine whether Etanercept (Enbrel) when used in conjunction with IVIG and aspirin, improves treatment response to IVIG in patients with Kawasaki Disease. Funding Source- FDA/OOPD Read more about this study
- Who is it for?
- Ages 2 months to 20 years
- Conditions the study is for
- Mucocutaneous Lymph Node Syndrome, Kawasaki Disease
- What is being tested?
- Etanercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 205 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Mar 2009to 30 Aug 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male Age 2 months to 20 years of age Female Age 2 months to 11 years of age
- Provision of Parental Consent
- Kawasaki Disease Presentation
Who cannot join
- Laboratory Criteria: Any laboratory toxicity, at the time of the screening visit or at any time during the study that in the opinion of the Investigator would preclude participation in the study or:
- Platelet count < 100,000/mm3
- WBC count < 3,000 cells/mm3
- Hemoglobin, hematocrit, or red blood cell count outside 30% of the upper or lower limits of normal for the Lab
- Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.
- Female subjects diagnosed with KD 12 years of age and older.
Show all 21Show fewer
- Subjects who have known hypersensitivity to Enbrel or any of its components or who is known to have antibodies to etanercept
- Prior or concurrent cyclophosphamide therapy
- Prior treatment with any TNF alpha antagonist or steroid within 48 hours prior to initiation of IVIG
- Concurrent sulfasalazine therapy
- Active severe infections within 4 weeks before screening visit, or between the screening and baseline visits.
- SLE, history of multiple sclerosis, transverse myelitis, optic neuritis, or chronic seizure disorder
- Known HIV-positive status or known history of any other immuno-suppressing disease.
- Any mycobacterial disease or high risk factors for tuberculosis, such as family member with TB or taking INH
- Untreated Lyme disease
- Severe comorbidities (diabetes mellitus requiring insulin, CHF of any severity, MI, CVA or TIA within 3 months of screening visit, unstable angina pectoris, uncontrolled hypertension (sitting systolic BP > 160 or diastolic BP > 100 mm Hg), oxygen-dependent severe pulmonary disease, history of cancer within 5 years [other than resected cutaneous basal or squamous cell carcinoma or in situ cervical cancer])
- Exposure to hepatitis B or hepatitis C or high risk factors such as intravenous drug abuse in patient's mother, or history of jaundice (other than neonatal jaundice). SLE, history of multiple sclerosis, transverse myelitis, optic neuritis or chronic seizure disorder.
- Use of a live vaccine (Measles Mumps Rubella or Varicella) 30 days prior to or during this study.
- Any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient
- History of non-compliance with other therapies
- Must not have received immunosuppressive agents for at least three months prior to enrollment.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53201
Feinstein Institute for Medical Rsearch
New Hyde Park, New York, 11040
Columbia University Medical Center
New York, New York, 10032
Primary Children's Medical Center
Salt Lake City, Utah, 84113
Seattle Children's Hospital
Seattle, Washington, 98105
Montefiore Medical Center
The Bronx, New York, 10467
About this study
Official title: A Randomized, Double Blind, Placebo Controlled Study of the Effects of Etanercept in Children Presenting With Kawasaki Disease
The purpose of this study is to determine whether Etanercept (Enbrel) when used in conjunction with IVIG and aspirin, improves treatment response to IVIG in patients with Kawasaki Disease. Funding Source- FDA/OOPD
Read the detailed description
Kawasaki Disease (KD) is a potentially life threatening acute vasculitis in children with a predilection for involvement of the coronary arteries. Aspirin and Intravenous gamma globulin (IVIG) are principally used for the treatment of the symptoms of Kawasaki Disease. Aspirin reduces inflammation and platelet formation, but has no effect in attenuating the development of coronary abnormalities. Although IVIG reduces inflammation and the prevalence of coronary artery abnormalities, it has a relatively high failure rate of 23-30%, warranting new treatment methods for Kawasaki Disease. We propose a placebo controlled double blinded randomized study to determine if etanercept 0.8 mg/kg subcutaneously (max 25 mg) given three times at weekly intervals starting at initial diagnosis is safe in this patient population and if it is a successful adjunct therapy with IVIG in reducing the incidence of persistent or recurrent fever.
- Being tested
- Etanercept, Placebo
- Keywords
- Etanercept
- Medical subject headings
- Mucocutaneous Lymph Node Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptDrug
Also called Enbrel
etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
PlaceboDrug
Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 -Etanercept | Experimental | Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin Receives: Drug: Etanercept |
| 2 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
IVIG Refractory
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.
Measured: 42 days after initial dose
Secondary outcomes (1)
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
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.
Measured: 42 days after initial dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2009 (estimated)
- Study startMar 2009
- Primary completionJan 2018
- Study completion30 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mucocutaneous Lymph Node SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Approximately 200 subjects will be randomized in a 1:1 ratio to receive Etanercept or Placebo. Subjects are randomized after hospital admission and diagnosis of Kawasaki Disease at eight participating sites. The primary analysis time-point is visit 5 (day 44). Sample size calculation is based on initial IVIG refractory rate at Seattle Children's. Assuming a 17.4% refractory rate in the control group and a 4.3% refractory rate in the Etanercept group, 200 subjects will provide 80% power at a 5% 2-sided type I error rate. Analyses will be based on a modified intention to treat population, including all subjects who were randomized and received at least 1 dose of study drug. Efficacy analyses will be based on randomization assignment, and safety analyses will be based on the treatment actually received. The statistical analysis plan will be finalized prior to database lock and study unblinding.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 205 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Portman
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, Michael Portman, Seattle Children's Hospital
- Investigators
- Michael A Portman, MD, Principal investigator, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841789
- Sponsor's protocol ID
- SEA-12652
- Other IDs
- FD003526
- Status last verified
- Apr 2023
- First submitted
- 10 Feb 2009
- Last updated
- 6 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Portman MA, Olson A, Soriano B, Dahdah N, Williams R, Kirkpatrick E. Etanercept as adjunctive treatment for acute Kawasaki disease: study design and rationale. Am Heart J. 2011 Mar;161(3):494-9. doi: 10.1016/j.ahj.2010.12.003.
PubMed 21392603Portman MA, Dahdah NS, Slee A, Olson AK, Choueiter NF, Soriano BD, Buddhe S, Altman CA; EATAK Investigators. Etanercept With IVIg for Acute Kawasaki Disease: A Randomized Controlled Trial. Pediatrics. 2019 Jun;143(6):e20183675. doi: 10.1542/peds.2018-3675. Epub 2019 May 2.
PubMed 31048415Sagiv E, Slee A, Buffone A, Choueiter NF, Dahdah NS, Portman MA. Etanercept with IVIg for acute Kawasaki disease: a long-term follow-up on the EATAK trial. Cardiol Young. 2023 Apr;33(4):613-618. doi: 10.1017/S1047951122001470. Epub 2022 May 12.
PubMed 35545881
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo Controlled Study of the Effects of Etanercept in Children Presenting With Kawasaki Disease
- ClinicalTrials.gov ID
- NCT00841789
- Acronym / sponsor ID
- SEA-12652
- Keywords
- Etanercept
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 205 participants (actual)
- Lead sponsor
- Michael PortmanUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Mar 2009
- Primary completion
- Jan 2018 (actual)
- Study completion
- 30 Aug 2018 (actual)
- First posted
- 11 Feb 2009 (estimated)
- Results
- Posted 6 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether Etanercept (Enbrel) when used in conjunction with IVIG and aspirin, improves treatment response to IVIG in patients with Kawasaki Disease. Funding Source- FDA/OOPD
Detailed description
Kawasaki Disease (KD) is a potentially life threatening acute vasculitis in children with a predilection for involvement of the coronary arteries. Aspirin and Intravenous gamma globulin (IVIG) are principally used for the treatment of the symptoms of Kawasaki Disease. Aspirin reduces inflammation and platelet formation, but has no effect in attenuating the development of coronary abnormalities. Although IVIG reduces inflammation and the prevalence of coronary artery abnormalities, it has a relatively high failure rate of 23-30%, warranting new treatment methods for Kawasaki Disease. We propose a placebo controlled double blinded randomized study to determine if etanercept 0.8 mg/kg subcutaneously (max 25 mg) given three times at weekly intervals starting at initial diagnosis is safe in this patient population and if it is a successful adjunct therapy with IVIG in reducing the incidence of persistent or recurrent fever.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Approximately 200 subjects will be randomized in a 1:1 ratio to receive Etanercept or Placebo. Subjects are randomized after hospital admission and diagnosis of Kawasaki Disease at eight participating sites. The primary analysis time-point is visit 5 (day 44). Sample size calculation is based on initial IVIG refractory rate at Seattle Children's. Assuming a 17.4% refractory rate in the control group and a 4.3% refractory rate in the Etanercept group, 200 subjects will provide 80% power at a 5% 2-sided type I error rate. Analyses will be based on a modified intention to treat population, including all subjects who were randomized and received at least 1 dose of study drug. Efficacy analyses will be based on randomization assignment, and safety analyses will be based on the treatment actually received. The statistical analysis plan will be finalized prior to database lock and study unblinding.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 -Etanercept | Experimental | Drug: EtanerceptDrug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin |
| 2 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 2 months to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Male Age 2 months to 20 years of age Female Age 2 months to 11 years of age
- Provision of Parental Consent
- Kawasaki Disease Presentation
Key exclusion criteria (21 listed)
- Laboratory Criteria: Any laboratory toxicity, at the time of the screening visit or at any time during the study that in the opinion of the Investigator would preclude participation in the study or:
- Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.
- Female subjects diagnosed with KD 12 years of age and older.
- Subjects who have known hypersensitivity to Enbrel or any of its components or who is known to have antibodies to etanercept
- Prior or concurrent cyclophosphamide therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtanerceptAlso: Enbreletanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis. | Drug | Arm 1 -Etanercept |
| PlaceboPlacebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis. | Drug | 2 |
Primary outcome
IVIG Refractory
Time frame: 42 days after initial dose
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.
1 secondary outcome
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
Time frame: 42 days after initial dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21392603Portman MA, Olson A, Soriano B, Dahdah N, Williams R, Kirkpatrick E. Etanercept as adjunctive treatment for acute Kawasaki disease: study design and rationale. Am Heart J. 2011 Mar;161(3):494-9. doi: 10.1016/j.ahj.2010.12.003.
- Results publication: PubMed 31048415Portman MA, Dahdah NS, Slee A, Olson AK, Choueiter NF, Soriano BD, Buddhe S, Altman CA; EATAK Investigators. Etanercept With IVIg for Acute Kawasaki Disease: A Randomized Controlled Trial. Pediatrics. 2019 Jun;143(6):e20183675. doi: 10.1542/peds.2018-3675. Epub 2019 May 2.
- Results publication: PubMed 35545881Sagiv E, Slee A, Buffone A, Choueiter NF, Dahdah NS, Portman MA. Etanercept with IVIg for acute Kawasaki disease: a long-term follow-up on the EATAK trial. Cardiol Young. 2023 Apr;33(4):613-618. doi: 10.1017/S1047951122001470. Epub 2022 May 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael A Portman, MD principal investigator
Seattle Children's Hospital
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etanercept in people with Mucocutaneous Lymph Node Syndrome and Kawasaki Disease, run by Michael Portman at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IVIG Refractory (time frame: 42 days after initial dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00841789, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.