Dataset Information

Study design and rationale to assess Doxycycline Efficacy in preventing coronary Artery Lesions in children with Kawasaki disease (DEAL trial) - A phase II clinical trial.

ABSTRACT:

Background

Kawasaki disease (KD) is the most common acquired heart disease in children of the developed world, and triggers progressive coronary artery lesions (CAL) in 30% of cases if left untreated. Despite standard anti-inflammatory treatment for KD, CAL (dilation or aneurysm) still occurs in 5-10% of children, increasing their risk for fatal coronary artery complications. CAL is mediated by enhanced matrix metalloproteinase activity and elastin breakdown induced by the inflammatory process in the coronary artery wall. Doxycycline is an effective inhibitor of matrix metalloproteinases, and has been shown to reduce elastin breakdown and CAL in a mouse model of KD, but has not been evaluated in patients.

Objective

We aim to evaluate the efficacy of doxycycline in the prevention of CAL in children during the acute phase of KD.

Design

This is a phase II prospective, randomized, double-blinded, clinical trial in two steps. In Step 1, any child older than 1month with the diagnosis of KD will be included. Children with KD will be included in Step 2 if they develop coronary artery dilation (z-score≥2.5) within 20days from the onset of fever. Study subjects in Step 2 will be randomized to receive a 3-week course of doxycycline or placebo.

Evaluation

The efficacy of a 3-week doxycycline course during the acute phase of KD will be evaluated by measuring the decline in coronary artery z-scores from baseline with doxycycline treatment compared to placebo.

Clinical trial registration

This study was registered on clinicaltrials.gov (NCT01917721).

SUBMITTER: Bratincsak A

PROVIDER: S-EPMC5803379 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

Study design and rationale to assess Doxycycline Efficacy in preventing coronary Artery Lesions in children with Kawasaki disease (DEAL trial) - A phase II clinical trial.

Bratincsak Andras A Limm-Chan Blair N BN Nerurkar Vivek R VR Ching Lauren L LL Reddy Venu D VD Lim Eunjung E Shohet Ralph V RV Melish Marian E ME

Contemporary clinical trials 20171205

<h4>Background</h4>Kawasaki disease (KD) is the most common acquired heart disease in children of the developed world, and triggers progressive coronary artery lesions (CAL) in 30% of cases if left untreated. Despite standard anti-inflammatory treatment for KD, CAL (dilation or aneurysm) still occurs in 5-10% of children, increasing their risk for fatal coronary artery complications. CAL is mediated by enhanced matrix metalloproteinase activity and elastin breakdown induced by the inflammatory p ...[more]

PMID: 29313803

Similar Datasets

Project description:BackgroundAlbumin (ALB) level is closely associated with the occurrence of intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD). The association between ALB level and CALs progression, is critical to the prognosis of KD patients. But little is known about it. This study aims to investigate the effect of the ALB level on CALs progression in KD patients.MethodsA total of 3,479 KD patients from 1 January 2005 to 30 November 2020, in Wenzhou, China were recruited. A total of 319 KD patients who had CALs and ALB data, and finish the follow-up as requested were enrolled in this study. They were classified into the low ALB group and the normal ALB group, divided by 30 g/L. CALs outcomes were classified into two categories according to the CALs changes from the time that CALs were detected within 48 h before or after IVIG treatment to 1 month after disease onset: progressed and no progressed. Multiple logistic regression models were used to assess the independent effect of ALB level on CALs progression among KD patients. Stratified analysis was performed to verify the ALB level on CALs progression among patients in different subgroups.ResultsHigher proportion of IVIG resistance (P < 0.001), receiving non-standard therapy (P < 0.001), and receiving delayed IVIG treatment (P = 0.020) were detected in patients with lower ALB level. Patients with lower ALB level had higher C-reactive protein (CRP) level (P = 0.097) and white blood cell count (WBC) (P = 0.036). After adjustment for confounders, patients with lower ALB level had higher odds of CALs progression; the adjusted odds ratio (OR) was 3.89 (95% CI: 1.68, 9.02). Similar results were found using stratification analysis and sensitivity analysis. Male gender and age over 36 months, as covariates in multiple logistic regression models, were also associated with CALs progression.ConclusionLow ALB level is identified as an independent risk factor for CALs progression in KD patients. Male gender and age over 36 months are also proved to be risk factors for CALs progression. Further investments are required to explore its mechanisms.

Dataset Information

Study design and rationale to assess Doxycycline Efficacy in preventing coronary Artery Lesions in children with Kawasaki disease (DEAL trial) - A phase II clinical trial.

Background

Objective

Design

Evaluation

Clinical trial registration

Publications

Study design and rationale to assess Doxycycline Efficacy in preventing coronary Artery Lesions in children with Kawasaki disease (DEAL trial) - A phase II clinical trial.

Similar Datasets

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