Doxycycline Treatment to Prevent Progressive Coronary Artery Dilation in Children With Kawasaki Disease

NCT01917721 | Active Not Recruiting Phase 2 Results

• 1 other identifier: 2013-005
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Kawasaki disease (KD) affects infants and young children causing inflammation of the skin and blood vessels including the coronary arteries of the heart. Despite the currently available therapy, about one third of children develop enlargement of the coronary arteries that can lead to serious complications such as coronary artery stenosis, heart attack and even death. Kawasaki disease is the most common heart disease in children in the USA and it is especially common among the children of Hawaii. Every year, 50-90 children are diagnosed with KD in Hawaii and unfortunately there is no medication available to successfully prevent coronary artery damage in a subset of cases. During the first few weeks of the illness, cells of the immune system attack the coronary arteries and release a special substance (MMP) that is responsible for the coronary artery enlargement. There is a common antibiotic, doxycycline that can specifically block the action of this special substance (MMP). Research done on animals with KD showed that doxycycline was able to block this special substance and prevent enlargement of coronary arteries. Research in adults with enlargement of the main artery in their abdomen also showed that doxycycline may improve the outcome. Based on these studies doxycycline may be a promising therapy for children with KD, who develop enlargement of the coronary arteries. The investigators' proposed research study will assess the usefulness of doxycycline in preventing the progressive enlargement of coronary arteries in children with KD. The investigators plan to perform a small (pilot) study to evaluate how good is doxycycline in preventing coronary artery enlargement. The investigators will treat 50 children with KD and enlarged coronary arteries for three weeks with doxycycline and assess the change in coronary arteries as well as the blood levels of the special substance (MMP). If doxycycline proves to be beneficial in this small study, the investigators are going to design a large research study involving multiple institutions on Hawaii and the mainland and will recruit more children to be certain about the value of the proposed treatment. The investigators' proposal may change the treatment protocol of KD and could present a possible treatment for children with enlarged coronary arteries preventing potentially devastating consequences.

Conditions

Kawasaki Disease; Coronary Aneurysm

Keywords

Kawasaki disease; doxycycline; coronary artery aneurysm

Outcome Measures

Primary Outcomes (1)

• Coronary Artery Diameter Z-score Change

  We will assess the Z-score change (decrease of the Z-scores expressed as a positive number) of the coronary artery diameter measurements from the acute phase to the convalescent phase of the disease (average 4 weeks, range 3-8 weeks). Z-scores of the coronary arteries correspond to coronary artery diameter values measured in mm. A Z-score of 0 corresponds to the mean of the population. A Z-score higher than 0 corresponds to a coronary artery diameter larger than that of the mean. A Z-score exceeding 2 identifies coronary arteries that are considered dilated/abnormal. A Z-score exceeding 2.5 identifies coronary artery aneurysms. A Z-score change of 1 corresponds to a decrease of the Z-score of coronary arteries by 1 standard deviation.

  From the acute phase of the disease to the convalescent phase of the disease (average 4 weeks, range 3-8 weeks)

Secondary Outcomes (2)

• Assess the Change in MMP-9 Level

  3 weeks

• Assess a Change in TIMP Level

  3 weeks

Study Arms (2)

Doxycycline

EXPERIMENTAL

These patients will receive doxycycline at the acute phase of their disease

Drug: Doxycycline

Placebo

ACTIVE COMPARATOR

The comparative arm of the study will receive standard care and placebo for Kawasaki disease, but not doxycycline

Drug: Placebo

Interventions

Doxycycline DRUG

The interventional arm of the study will receive doxycycline 4.4 mg/kg/day for 21 days besides receiveing standard care: IVIG and/or Remicade.

Doxycycline

Placebo DRUG

Standard medical care and placebo will be provided to the comparative arm of the study administering IVIG and/or Remicade, but not doxycycline.

Also known as: IVIG and Remicade

Placebo

Eligibility Criteria

• Age: 1 Month - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Treatment arm: Patients aged 1 month to 21 years with confirmed KD will be included in the study if they meet the following criteria:
• Patients with dilation of the right or left anterior descending coronary artery beyond a z-score of +2.5 during the acute febrile phase of KD.
• Patients with aneurysms of the right or left main coronary arteries during the acute febrile phase of KD.
• Patients with refractory KD after initial treatment with IVIG and dilated coronary arteries on an echocardiogram during the first month of KD.
• Patients with right or left anterior descending coronary artery measurements below a z-score of +2.5 during the acute febrile phase of KD.

You may not qualify if:

• The following patients will be excluded from this study:
• Patients with clinically incomplete KD.
• Patients whose parents refuse to administer doxycycline.
• Patients with acute renal failure.
• Patients with chronic liver and kidney disease.

Sponsors & Collaborators

• Hawaii Pacific Health: lead

Study Sites (1)

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Related Publications (1)

• Bratincsak A, Limm-Chan BN, Nerurkar VR, Ching LL, Reddy VD, Lim E, Shohet RV, Melish ME. 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. Contemp Clin Trials. 2018 Feb;65:33-38. doi: 10.1016/j.cct.2017.11.014. Epub 2017 Dec 5.

  PMID: 29313803 DERIVED

MeSH Terms

Conditions

Mucocutaneous Lymph Node Syndrome; Coronary Aneurysm

Interventions

Doxycycline; Immunoglobulins, Intravenous; Infliximab

Condition Hierarchy (Ancestors)

Vasculitis; Vascular Diseases; Cardiovascular Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Aneurysm

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal

Results Point of Contact

• Title: Dr. Andras Bratincsak
• Organization: Hawaii Pacific Health

andrasb@hphmg.org

808-983-6000

Study Officials

• Andras Bratincsak, MD PhD

  Hawaii Pacific Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: April 26, 2013
• First Posted: August 7, 2013
• Study Start: October 1, 2013
• Primary Completion: February 1, 2026
• Study Completion: August 1, 2026
• Last Updated: June 3, 2026
• Results First Posted: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)