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

May 7, 2026 updated by: Andras Bratincsak, MD, PhD, Hawaii Pacific Health

Phase 2 Study to Assess the Efficacy and Safety of Doxycycline in Preventing Coronary Artery Aneurysm Formation and Progression

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This research study attempts to reveal whether coronary artery dilation in patients with Kawasaki disease refractory to standard therapy could be prevented using a matrix metalloproteinase inhibitor: doxycycline.

Hypothesis The investigators hypothesize that oral administration of doxycycline for two weeks during the acute phase of Kawasaki disease (KD) effectively blocks matrix metalloproteinase-9 (MMP-9) activity in the coronary arteries and therefore prevents the progression of coronary artery dilation and aneurysm formation in children with KD.

Rationale There is no specific treatment for children with KD, who develop coronary artery dilation or aneurysm. Based on the animal studies and adult trials showing beneficial effect of doxycycline on coronary artery dilation and abdominal aneurysms, this selective MMP-9 inhibitor offers a promising therapeutic strategy to prevent progressive coronary artery dilation in children with KD.

Specific aims

  1. Measure serum MMP-9 activity, tissue inhibitor of metalloproteinase 1 activity (TIMP-1), serum levels of degradation products due to MMP-9 activity (elastin and gelatin degradation products) before and after treatment with doxycycline in children with KD.
  2. Compare serum MMP-9 activity and degradation product levels of children receiving only standard therapy for KD (IVIG, infliximab) with children receiving standard therapy and doxycycline treatment.
  3. Measure the coronary artery diameters before and after doxycycline treatment in children with KD.
  4. Compare coronary artery measurements of children receiving only standard therapy for KD (IVIG, infliximab) with children receiving standard therapy and doxycycline treatment.
  5. Design a multi-center prospective randomized blinded placebo-controlled trial to assess the efficacy of doxycycline in preventing coronary artery dilation and aneurysm.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Hawaii
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Treatment arm: Patients aged 1 month to 21 years with confirmed KD will be included in the study if they meet the following criteria:

  1. 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.
  2. Patients with aneurysms of the right or left main coronary arteries during the acute febrile phase of KD.
  3. Patients with refractory KD after initial treatment with IVIG and dilated coronary arteries on an echocardiogram during the first month of KD.

Comparison arm: Patients aged 1 month to 18 years with confirmed KD, who do not meet inclusion criteria to be included in the treatment group.

1.Patients with right or left anterior descending coronary artery measurements below a z-score of +2.5 during the acute febrile phase of KD.

Exclusion Criteria:

The following patients will be excluded from this study:

  1. Patients with clinically incomplete KD.
  2. Patients whose parents refuse to administer doxycycline.
  3. Patients with acute renal failure.
  4. Patients with chronic liver and kidney disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Doxycycline
These patients will receive doxycycline at the acute phase of their disease
Drug: Doxycycline
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.
Active Comparator: Placebo
The comparative arm of the study will receive standard care and placebo for Kawasaki disease, but not doxycycline
Drug: Placebo
Standard medical care and placebo will be provided to the comparative arm of the study administering IVIG and/or Remicade, but not doxycycline.
Other Names:
  • IVIG and Remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coronary Artery Diameter Z-score Change
Time Frame: From the acute phase of the disease to the convalescent phase of the disease (average 4 weeks, range 3-8 weeks)

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the Change in MMP-9 Level
Time Frame: 3 weeks
We will draw blood samples before, during and after the administration of doxycyline to assess the effect on MMP-9 (matrix metalloproteinase 9).
3 weeks
Assess a Change in TIMP Level
Time Frame: 3 weeks
We will draw blood samples before, during and after the administration of doxycyline to assess the effect on MMP-9 (matrix metalloproteinase 9) and TIMP (tissue inhibitor of matrix metalloproteinase).
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hawaii Pacific Health

Investigators

  • Principal Investigator: Andras Bratincsak, MD PhD, Hawaii Pacific Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2013

Primary Completion (Actual)

February 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

April 26, 2013

First Submitted That Met QC Criteria

August 5, 2013

First Posted (Estimated)

August 7, 2013

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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