Kawasaki DiseasePhase 2NCT01917721
Doxycycline Treatment to Prevent Progressive Coronary Artery Dilation in Children With Kawasaki Disease
A Phase 2 study testing Doxycycline in people with Kawasaki Disease and Coronary Aneurysm, run by Hawaii Pacific Health at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 month to 21 years
- Conditions the study is for
- Kawasaki Disease, Coronary Aneurysm
- What is being tested?
- Doxycycline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Aug 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
About this study
Official title: 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.
Read more
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.
Read the 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
- 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.
- 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.
- Measure the coronary artery diameters before and after doxycycline treatment in children with KD.
- Compare coronary artery measurements of children receiving only standard therapy for KD (IVIG, infliximab) with children receiving standard therapy and doxycycline treatment.
- Design a multi-center prospective randomized blinded placebo-controlled trial to assess the efficacy of doxycycline in preventing coronary artery dilation and aneurysm.
- Conditions
- Kawasaki Disease, Coronary Aneurysm
- Being tested
- Doxycycline, Placebo
- Keywords
- Kawasaki disease, doxycycline, coronary artery aneurysm
- Medical subject headings
- Mucocutaneous Lymph Node Syndrome, Coronary Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
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.
PlaceboDrug
Also called IVIG and Remicade
Standard medical care and placebo will be provided to the comparative arm of the study administering IVIG and/or Remicade, but not doxycycline.
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline | Experimental | These patients will receive doxycycline at the acute phase of their disease Receives: Drug: Doxycycline |
| Placebo | Active comparator | The comparative arm of the study will receive standard care and placebo for Kawasaki disease, but not doxycycline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
We will draw blood samples before, during and after the administration of doxycyline to assess the effect on MMP-9 (matrix metalloproteinase 9).
Measured: 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).
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2013 (estimated)
- Study startOct 2013
- Primary completionFeb 2026
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kawasaki DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hawaii Pacific Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andras Bratincsak, MD, PhD, Hawaii Pacific Health
- Investigators
- Andras Bratincsak, MD PhD, Principal investigator, Hawaii Pacific Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01917721
- Sponsor's protocol ID
- 2013-005
- Status last verified
- May 2026
- First submitted
- 26 Apr 2013
- Last updated
- 3 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 29313803