A Phase 2 interventional study of Doxycycline and Placebo in Kawasaki Disease and Coronary Aneurysm, sponsored by Hawaii Pacific Health. Active, not recruiting at 1 site in United States. Open to participants aged 1 Month to 21 Years. Per ClinicalTrials.gov, last updated 2026-06-03.
Sponsored by Hawaii Pacific Health · Phase 2, Interventional, and Treatment
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.
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
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This study's enrollment of 26 is below the median of 45 across 35 interventional studies indexed under Mucocutaneous Lymph Node Syndrome.
Browse Mucocutaneous Lymph Node Syndrome studies →Hawaii Pacific Health is the lead sponsor of 8 studies on the registry; 1 is open to participants now.
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Treatment arm: Patients aged 1 month to 21 years with confirmed KD will be included in the study if they meet the following criteria:
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:
These patients will receive doxycycline at the acute phase of their disease
Drug: Doxycycline
The comparative arm of the study will receive standard care and placebo for Kawasaki disease, but not doxycycline
Drug: Placebo
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.
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
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.
Time frame: From the acute phase of the disease to the convalescent phase of the disease (average 4 weeks, range 3-8 weeks)
Assess the Change in MMP-9 Level
We will draw blood samples before, during and after the administration of doxycyline to assess the effect on MMP-9 (matrix metalloproteinase 9).
Time frame: 3 weeks
Assess a Change in TIMP Level
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).
Time frame: 3 weeks
| Milestone | Doxycycline | Placebo |
|---|---|---|
| Started | 15 | 11 |
| Completed | 14 | 11 |
| Not completed | 1 | 0 |
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.
| Z-score | Doxycycline | Placebo |
|---|---|---|
| RCA (right coronary artery) | 1.56 (0.10 to 2.25) | 1.25 (0.71 to 1.99) |
| LAD (left anterior descending coronary artery) | 1.45 (1.22 to 2.49) | 1.98 (0.81 to 3.84) |
We will draw blood samples before, during and after the administration of doxycyline to assess the effect on MMP-9 (matrix metalloproteinase 9).
| microgram / mililiter | Doxycycline | Placebo |
|---|---|---|
| Assess the Change in MMP-9 Level | 90 (50 to 120) | 80 (50 to 100) |
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).
| microgram / mililiter | Doxycycline | Placebo |
|---|---|---|
| Assess a Change in TIMP Level | 105 (90 to 115) | 115 (95 to 120) |
Collected over 24 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Doxycycline | 0/15 (0%) | 0/15 (0%) | 10/15 (66.7%) |
| Placebo | 0/11 (0%) | 0/11 (0%) | 5/11 (45.5%) |
| Event | Doxycycline | Placebo |
|---|---|---|
| Respiratory InfectionRespiratory, thoracic and mediastinal disorders | 4/15 | 3/11 |
| RashSkin and subcutaneous tissue disorders | 3/15 | 2/11 |
| FeverGeneral disorders | 2/15 | 2/11 |
| Sun sensitivitySkin and subcutaneous tissue disorders | 1/15 | 0/11 |
| Chest painCardiac disorders | 1/15 | 0/11 |
| Age, Continuous(years) | Doxycycline | Placebo | Total |
|---|---|---|---|
| Median | 2.22 (.48 to 4.18) | 2.09 (.77 to 4.53) | 2.21 (.3 to 6.14) |
| Sex: Female, Male(Participants) | Doxycycline | Placebo | Total |
|---|---|---|---|
| Female | 8 | 3 | 11 |
| Male | 7 | 8 | 15 |
| Race (NIH/OMB)(Participants) | Doxycycline | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 6 | 5 | 11 |
| Native Hawaiian or Other Pacific Islander | 2 | 0 | 2 |
| Black or African American | 0 | 0 | 0 |
| White | 0 | 0 | 0 |
| More than one race | 7 | 6 | 13 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Doxycycline | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 2 |
| Not Hispanic or Latino | 14 | 10 | 24 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Doxycycline | Placebo | Total |
|---|---|---|---|
| United States | 15 | 11 | 26 |
| Coronary Artery Dilation(Z-score) | Doxycycline | Placebo | Total |
|---|---|---|---|
| RCA (right coronary artery) | 2.51 (0.62 to 3.24) | 2.42 (1.38 to 3.52) | 2.47 (0.7 to 3.44) |
| LAD (left anterior descending coronary artery) | 3.36 (2.79 to 4.24) | 2.76 (1.86 to 4.08) | 3.3 (2.25 to 4.08) |
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