Kawasaki DiseasePhase 3NCT00760435
Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease
A Phase 3 study testing Infliximab in people with Kawasaki Disease, run by University of California, San Diego at 2 sites in United States.
Trial summary
The purpose of this study is to determine whether the addition of infliximab to standard primary therapy of intravenous immunoglobulin (IVIG) and high dose aspirin will reduce resistance to therapy in acute Kawasaki disease (KD). Read more about this study
- Who is it for?
- Ages 4 weeks to 17 years
- Conditions the study is for
- Kawasaki Disease
- What is being tested?
- Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 196 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2009to Oct 2012
- Phase
- Phase 3
- 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 4 weeks to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- All eligible subjects, or legal representative, must provide written informed consent/assent, prior to initiation of any study procedure.
- Eligible subjects will be infants and children, 4 weeks to 17 years old, who have had fever for 3 to 15 days (illness day 1 = first day of fever ≥ 38.3° C)
- Patients who meet one of the following sets of criteria will be eligible for enrollment (adapted from AHA guidelines: Newburger et al. 2004):
- Case definition for complete KD: Fever (≥ 38.3°C) for ≥ 3 days and 4/5 standard clinical criteria (Table 1)
- Case definition for incomplete KD: Fever ≥ 5 days and 2-3 clinical criteria plus either C-reactive protein (CRP) ≥ 3.0 mg/dL or ESR ≥40 mm/hr AND ≥ 3 supplemental laboratory criteria: albumin ≤ 3.0 g/dl, anemia for age, ALT ≥ 45, platelet count ≥ 450,000/mm3, white blood cell count ≥ 15,000/mm3, or urinalysis with ≥10 white blood cells/hpf.
- Case definition for incomplete KD with echocardiogram data: Fever ≥ 5 days and <4/5 clinical criteria plus abnormal echocardiogram with z score of LAD or RCA ≥ 2.5
- Females of childbearing potential and males must be using adequate contraception (abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) throughout the trial.
- All eligible subjects must have a chest radiograph within one week prior to first infusion of study drug with no evidence of tuberculosis or other infection.
Who cannot join
- Have been receiving corticosteroids (i.e. via any route) at doses > 1 mg/kg prednisone equivalent daily.
- History of tuberculosis (TB) or TB exposure.
- Have received a BCG vaccination within the past 6 months.
- History of histoplasmosis or coccidioidomycosis
- Have received anakinra (Kineret®), etanercept (Enbrel®), or adalimumab (Humira®) within 1 month prior to first study drug administration.
- Have any chronic disease, except asthma, atopic dermatitis or controlled seizure disorder.
Show all 21Show fewer
- Have documented history of current active Hepatitis B or a history of Hepatitis C infection.
- Have a documented history of human immunodeficiency virus (HIV) infection.
- Have received a transplanted organ (with the exception of a corneal transplant performed > 3 months prior to the first study drug administration).
- Have a known malignancy or history of malignancy within the 5-year period prior to first study drug administration (with the exception of basal cell or squamous cell carcinoma of the skin that has been completely excised without evidence of recurrence).
- Have a history of prior lymphoproliferative disease including lymphoma.
- Have multiple sclerosis or other central demyelinating disorder.
- Have received any previous treatment with infliximab or other monoclonal antibodies
- Have used any investigational drug within 1 month prior to first study drug administration or within 5 half-lives of the investigational agent, whichever is longer.
- Are participating in another investigative trial, involving investigational agents, during participation in this trial.
- Have a history of substance abuse (drug or alcohol) within the previous 3 years.
- Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter.
- Have a known allergy to murine proteins or other chimeric proteins.
- Patients with ischemic congestive heart failure, defined by ECG changes, elevated Troponin 1 and CPK-MB consistent with myocardial ischemia.
- Have an abnormal chest radiograph
- Afebrile for ≥ 48 hours
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Nationwide Children's Hospital
Columbus, Ohio
University of California, San Diego
La Jolla, California, 92093
About this study
Official title: Infliximab (Remicade®) Plus Intravenous Immunoglobulin (IVIG) for the Primary Treatment of Patients With Acute Kawasaki Disease
The purpose of this study is to determine whether the addition of infliximab to standard primary therapy of intravenous immunoglobulin (IVIG) and high dose aspirin will reduce resistance to therapy in acute Kawasaki disease (KD).
Read the detailed description
KD, an orphan disease of low prevalence in U.S. children, causes significant long term cardiac sequelae in a subset of patients. KD patients that are resistant to therapy are more likely to develop coronary artery abnormalities. This phase III placebo-controlled, multicenter, randomized clinical trial of infliximab plus standard therapy vs. placebo plus standard therapy in acute KD will determine if the addition of infliximab to primary therapy can reduce the percentage of children resistant to therapy.
- Conditions
- Kawasaki Disease
- Being tested
- Infliximab, Placebo
- Keywords
- Kawasaki disease, Infliximab, Remicade, Pediatrics
- 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.
InfliximabDrug
Also called Remicade
5 mg/kg IV over 2 hours once
PlaceboDrug
Placebo (same volume as active drug)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Infliximab plus Intravenous immunoglobulin (IVIG) Receives: Drug: Infliximab |
| 2 | Placebo comparator | Placebo plus IVIG Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Subjects in Each Arm That Have Persistent or Recrudescent Fever 24 Hours After Completion of the Intravenous Immunoglobulin (IVIG) Infusion
Measured: 10 weeks
Secondary outcomes (3)
Number of Days of Fever Following Therapy During Study Period (up to 6 Weeks)
Measured: up to 6 weeks
Change in C-reactive Protein (CRP) From Baseline at 24 Hours After Completion of Intravenous Immunoglobulin (IVIG) by Study Arm.
Measured: 24 hours
Change From Baseline in Left Anterior Descending Coronary Artery Outcomes at Week 2 by Treatment Arm
left anterior descending coronary artery Z-score; a Z score is the coronary artery adjusted for body surface area
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2008 (estimated)
- Study startMar 2009
- Primary completionOct 2012
- Study completionOct 2012
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 (8)Papers the sponsor has linked to this study.
- Other trials for Kawasaki DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Nationwide Children's Hospital
- Responsible party
- Principal investigator, Jane C. Burns, University of California, San Diego
- Investigators
- Jane C Burns, M.D., Principal investigator, University of California, San DiegoAdriana H. Tremoulet, M.D., Study director, University of California, San DiegoOctavio Ramilo, M.D., Study director, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00760435
- Sponsor's protocol ID
- 1R01FD003514-01
- Status last verified
- Nov 2014
- First submitted
- 25 Sep 2008
- Last updated
- 24 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS, Melish ME, Jackson MA, Asmar BI, Lang DJ, Connor JD, Capparelli EV, Keen ML, Mamun K, Keenan GF, Ramilo O. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease. J Pediatr. 2008 Dec;153(6):833-8. doi: 10.1016/j.jpeds.2008.06.011. Epub 2008 Jul 30.
PubMed 18672254Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, Martin DD, Newburger JW, Burns JC. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008 Jul;153(1):117-21. doi: 10.1016/j.jpeds.2007.12.021. Epub 2008 Mar 4.
PubMed 18571548Newburger JW, Sleeper LA, McCrindle BW, Minich LL, Gersony W, Vetter VL, Atz AM, Li JS, Takahashi M, Baker AL, Colan SD, Mitchell PD, Klein GL, Sundel RP; Pediatric Heart Network Investigators. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007 Feb 15;356(7):663-75. doi: 10.1056/NEJMoa061235.
PubMed 17301297Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004 Dec;114(6):1708-33. doi: 10.1542/peds.2004-2182.
PubMed 15574639Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD, Balfour I, Shen CA, Michel ED, Shulman ST, Melish ME. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005 May;146(5):662-7. doi: 10.1016/j.jpeds.2004.12.022.
PubMed 15870671Tremoulet AH, Jain S, Jaggi P, Jimenez-Fernandez S, Pancheri JM, Sun X, Kanegaye JT, Kovalchin JP, Printz BF, Ramilo O, Burns JC. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet. 2014 May 17;383(9930):1731-8. doi: 10.1016/S0140-6736(13)62298-9. Epub 2014 Feb 24.
PubMed 24572997Burns JC, Song Y, Bujold M, Shimizu C, Kanegaye JT, Tremoulet AH, Franco A. Immune-monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin. Clin Exp Immunol. 2013 Dec;174(3):337-44. doi: 10.1111/cei.12182.
PubMed 23901839Kanegaye JT, Van Cott E, Tremoulet AH, Salgado A, Shimizu C, Kruk P, Hauschildt J, Sun X, Jain S, Burns JC. Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr. 2013 Jun;162(6):1259-63, 1263.e1-2. doi: 10.1016/j.jpeds.2012.11.064. Epub 2013 Jan 7.
PubMed 23305955
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infliximab (Remicade®) Plus Intravenous Immunoglobulin (IVIG) for the Primary Treatment of Patients With Acute Kawasaki Disease
- ClinicalTrials.gov ID
- NCT00760435
- Acronym / sponsor ID
- 1R01FD003514-01
- Conditions
- Kawasaki Disease
- Keywords
- Kawasaki disease, Infliximab, Remicade, Pediatrics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Nationwide Children's Hospital
- Study start
- Mar 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 26 Sep 2008 (estimated)
- Results
- Posted 13 Nov 2014
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 the addition of infliximab to standard primary therapy of intravenous immunoglobulin (IVIG) and high dose aspirin will reduce resistance to therapy in acute Kawasaki disease (KD).
Detailed description
KD, an orphan disease of low prevalence in U.S. children, causes significant long term cardiac sequelae in a subset of patients. KD patients that are resistant to therapy are more likely to develop coronary artery abnormalities. This phase III placebo-controlled, multicenter, randomized clinical trial of infliximab plus standard therapy vs. placebo plus standard therapy in acute KD will determine if the addition of infliximab to primary therapy can reduce the percentage of children resistant to therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: InfliximabInfliximab plus Intravenous immunoglobulin (IVIG) |
| 2 | Placebo comparator | Drug: PlaceboPlacebo plus IVIG |
Who may qualify
- Ages
- 4 weeks to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- All eligible subjects, or legal representative, must provide written informed consent/assent, prior to initiation of any study procedure.
- Eligible subjects will be infants and children, 4 weeks to 17 years old, who have had fever for 3 to 15 days (illness day 1 = first day of fever ≥ 38.3° C)
- Patients who meet one of the following sets of criteria will be eligible for enrollment (adapted from AHA guidelines: Newburger et al. 2004):
- Females of childbearing potential and males must be using adequate contraception (abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) throughout the trial.
- All eligible subjects must have a chest radiograph within one week prior to first infusion of study drug with no evidence of tuberculosis or other infection.
Key exclusion criteria (21 listed)
- Have been receiving corticosteroids (i.e. via any route) at doses > 1 mg/kg prednisone equivalent daily.
- History of tuberculosis (TB) or TB exposure.
- Have received a BCG vaccination within the past 6 months.
- History of histoplasmosis or coccidioidomycosis
- Have received anakinra (Kineret®), etanercept (Enbrel®), or adalimumab (Humira®) within 1 month prior to first study drug administration.
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 |
|---|---|---|
| InfliximabAlso: Remicade5 mg/kg IV over 2 hours once | Drug | 1 |
| PlaceboPlacebo (same volume as active drug) | Drug | 2 |
Primary outcome
The Number of Subjects in Each Arm That Have Persistent or Recrudescent Fever 24 Hours After Completion of the Intravenous Immunoglobulin (IVIG) Infusion
Time frame: 10 weeks
3 secondary outcomes
Number of Days of Fever Following Therapy During Study Period (up to 6 Weeks)
Time frame: up to 6 weeks
Change in C-reactive Protein (CRP) From Baseline at 24 Hours After Completion of Intravenous Immunoglobulin (IVIG) by Study Arm.
Time frame: 24 hours
Change From Baseline in Left Anterior Descending Coronary Artery Outcomes at Week 2 by Treatment Arm
Time frame: 2 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18672254Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS, Melish ME, Jackson MA, Asmar BI, Lang DJ, Connor JD, Capparelli EV, Keen ML, Mamun K, Keenan GF, Ramilo O. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease. J Pediatr. 2008 Dec;153(6):833-8. doi: 10.1016/j.jpeds.2008.06.011. Epub 2008 Jul 30.
- Background: PubMed 18571548Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, Martin DD, Newburger JW, Burns JC. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008 Jul;153(1):117-21. doi: 10.1016/j.jpeds.2007.12.021. Epub 2008 Mar 4.
- Background: PubMed 17301297Newburger JW, Sleeper LA, McCrindle BW, Minich LL, Gersony W, Vetter VL, Atz AM, Li JS, Takahashi M, Baker AL, Colan SD, Mitchell PD, Klein GL, Sundel RP; Pediatric Heart Network Investigators. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007 Feb 15;356(7):663-75. doi: 10.1056/NEJMoa061235.
- Background: PubMed 15574639Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004 Dec;114(6):1708-33. doi: 10.1542/peds.2004-2182.
- Background: PubMed 15870671Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD, Balfour I, Shen CA, Michel ED, Shulman ST, Melish ME. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005 May;146(5):662-7. doi: 10.1016/j.jpeds.2004.12.022.
- Derived from this study: PubMed 24572997Tremoulet AH, Jain S, Jaggi P, Jimenez-Fernandez S, Pancheri JM, Sun X, Kanegaye JT, Kovalchin JP, Printz BF, Ramilo O, Burns JC. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet. 2014 May 17;383(9930):1731-8. doi: 10.1016/S0140-6736(13)62298-9. Epub 2014 Feb 24.
- Derived from this study: PubMed 23901839Burns JC, Song Y, Bujold M, Shimizu C, Kanegaye JT, Tremoulet AH, Franco A. Immune-monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin. Clin Exp Immunol. 2013 Dec;174(3):337-44. doi: 10.1111/cei.12182.
- Derived from this study: PubMed 23305955Kanegaye JT, Van Cott E, Tremoulet AH, Salgado A, Shimizu C, Kruk P, Hauschildt J, Sun X, Jain S, Burns JC. Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr. 2013 Jun;162(6):1259-63, 1263.e1-2. doi: 10.1016/j.jpeds.2012.11.064. Epub 2013 Jan 7.
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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.
Jane C Burns, M.D. principal investigator
University of California, San Diego
Adriana H. Tremoulet, M.D. study director
University of California, San Diego
Octavio Ramilo, M.D. study director
University of Texas
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Infliximab in people with Kawasaki Disease, run by University of California, San Diego at 2 sites in United States.
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 8 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 24 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 13 Nov 2014). 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?
The Number of Subjects in Each Arm That Have Persistent or Recrudescent Fever 24 Hours After Completion of the Intravenous Immunoglobulin (IVIG) Infusion (time frame: 10 weeks). 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 NCT00760435, which also lists 8 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 24 Nov 2014.