Browsing by Author "Michalik, David E."

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    Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial
    (Elsevier, 2021-12) Burns, Jane C.; Roberts, Samantha C.; Tremoulet, Adriana H.; He, Feng; Printz, Beth F.; Ashouri, Negar; Jain, Supriya S.; Michalik, David E.; Sharma, Kavita; Truong, Dongngan T.; Wood, James B.; Kim, Katherine K.; Jain, Sonia; Anand, Vikram; Anderson, Marsha; Ang, Jocelyn; Ansusinha, Emily; Arditi, Moshe; Bartlett, Allison; Baker, Annette; Chatterjee, Archana; DeBiasi, Roberta; De Ferranti, Sarah; Dekker, Cornelia; DeZure, Chandani; Dominguez, Samuel; Erdem, Guliz; Halasa, Natasha; Harahsheh, Ashraf S.; Hite, Michelle; Jaggi, Preeti; Jone, Pei-Ni; Jones, Jessica; Kaushik, Neeru; Kumar, Madan; Kurio, Gregory; Lloyd, David; Manaloor, John; McNelis, Amy; Nadipuram, Santhosh; Newburger, Jane; Newcomer, Charles; Perkins, Tiffany; Portman, Michael; Romero, José R.; Rometo, Allison; Ronis, Tova; Rosenkranz, Margalit; Rowley, Anne; Samuy, Nichole; Scalici, Paul; Schuster, Jennifer; Sexson Tejtel, S. Kristen; Simonsen, Kari; Szmuszkovicz, Jacqueline; Yeh, Sylvia; Pediatrics, School of Medicine
    Background Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10–20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease. Methods In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8–12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244. Findings Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13–0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p<0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only. Interpretation Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion.
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    The Kawasaki Disease Comparative Effectiveness (KIDCARE) trial: A phase III, randomized trial of second intravenous immunoglobulin versus infliximab for resistant Kawasaki disease
    (Elsevier, 2019-04) Roberts, Samantha C.; Jain, Sonia; Tremoulet, Adriana H.; Kim, Katherine K.; Burns, Jane C.; Anand, Vikram; Anderson, Marsha; Ang, Jocelyn; Ansusinha, Emily; Arditi, Moshe; Ashouri, Negar; Bartlett, Allison; Chatterjee, Archana; DeBiasi, Roberta; Dekker, Cornelia; DeZure, Chandani; Didion, Lisa; Dominguez, Samuel; El Feghaly, Rana; Erdem, Guliz; Halasa, Natasha; Harahsheh, Ashraf; Jackson, Mary Anne; Jaggi, Preeti; Jain, Supriya; Jone, Pei-Ni; Kaushik, Neeru; Kurio, Gregory; Lillian, Anna; Lloyd, David; Manaloor, John; McNelis, Amy; Michalik, David E.; Newburger, Jane; Newcomer, Charles; Perkins, Tiffany; Portman, Michael; Romero, Jose; Ronis, Tova; Rowley, Anne; Schneider, Kathryn; Schuster, Jennifer; Sexson Tejtel, S. Kristen; Sharma, Kavita; Simonsen, Kari; Szmuszkovicz, Jacqueline; Truong, Dongngan; Wood, James; Yeh, Sylvia; Pediatrics, School of Medicine
    Background Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10–20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients. Objectives The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience. Methods The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5–18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm. Conclusion This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments.