Pharmacokinetics (PK)/Safety Study of Atorvastatin in Children With Kawasaki Disease and Coronary Artery Abnormalities

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of California, San Diego
Sponsor:
Collaborators:
Children's Hospital Colorado
University of Colorado, Denver
Information provided by (Responsible Party):
Jane C. Burns, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01431105
First received: September 6, 2011
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

Kawasaki disease (KD) is the leading cause of acquired heart disease in children in the developed world. Despite available treatment, 25% of children in San Diego County appropriately treated for KD develop coronary artery abnormalities that could lead to complications later in life, including heart attack. Although investigators can identify children with KD that have these coronary artery abnormalities, there is no approved additional treatment to decrease coronary artery inflammation and arrest or prevent damage to the coronary arteries. Inflammation and damage to the arterial wall is central to these coronary artery abnormalities. Statins, a class of drugs that is known for lowering cholesterol, have also been shown to decrease inflammation in general as well as at the level of the vessel wall. Therefore, the investigators propose to study the safety of the drug atorvastatin in children with coronary artery abnormalities from KD.


Condition Intervention Phase
Kawasaki Disease
Drug: Atorvastatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/IIa Study of Pharmacokinetics and Safety of Atorvastatin in Children With Coronary Artery Abnormalities Secondary to Kawasaki Disease

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Safety of atorvastatin in children with coronary artery abnormalities secondary to Kawasaki disease [ Time Frame: At 6 weeks after initiation of study drug ] [ Designated as safety issue: Yes ]
    Evaluation of cholesterol, liver functions, and markers of myopathy at the above time points.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 0,1,2,6,12,24 hours at baseline; 2&6 weeks ] [ Designated as safety issue: No ]
    Blood will be drawn around the first dose at 0,1,2,6,12 and 24 hours and troughs will be drawn at 2 weeks and 6 weeks during the clinic visit.

  • Atorvastatin Activity [ Time Frame: Baseline, 2 weeks and 6 weeks ] [ Designated as safety issue: No ]
    Measures of oxidative stress will be assessed at baseline, 2 weeks and 6 weeks after study enrollment.


Estimated Enrollment: 32
Study Start Date: July 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvasatin
Atorvastatin dose titration to maximum tolerated dose
Drug: Atorvastatin
Atorvastatin dose titration to maximum tolerated dose (once daily for 6 weeks)
Other Name: Lipitor

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Age ≥ 2 years to 17 years old
  2. Meets clinical criteria for KD according to American Heart Association guidelines (Table 2): Fever (T≥38oC or 100.4oC) ≥ 3 days and ≥ 2 clinical criteria with left anterior descending coronary artery/right coronary artery z-score ≥ 2.5 or an aneurysm (≥ 1.5 x the adjacent segment) of one of the coronary arteries
  3. Patient presents within the first 20 days after fever onset
  4. Parent or legal guardian able and willing to provide informed consent and subject willing and able to provide assent when appropriate.
  5. Post-menarchal females: Negative pregnancy test at screening and willing to use two forms of contraception during the study
  6. Males engaging in sexual activity that could lead to pregnancy must use a condom.

Exclusion Criteria:

  1. Use of a statin, fibrate, or niacin within the 3 months prior to enrollment
  2. Have any chronic disease, except asthma, atopic dermatitis, autism or controlled seizure disorder
  3. Screening creatine phosphokinase (CK) ≥ 3x upper limit of normal for age
  4. Patient taking a CYP3A4 inhibitor (ie. cyclosporine or clarithromycin) in the last 7 days
  5. Patient has a history of allergy to atorvastatin or its derivatives
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431105

Contacts
Contact: Jane C Burns, MD 858-246-0155 jcburns@ucsd.edu
Contact: Adriana Tremoulet, MD, MAS 858-246-0012 atremoulet@ucsd.edu

Locations
United States, California
University of California San Diego Recruiting
San Diego, California, United States, 92093
Contact: Adriana H. Tremoulet, MD, MAS    858-246-0012    atremoulet@ucsd.edu   
Contact: Jane C. Burns, MD    858-246-0155    jcburns@ucsd.edu   
Principal Investigator: Jane C Burns, MD         
Sub-Investigator: Adriana H Tremoulet, MD         
Sponsors and Collaborators
University of California, San Diego
Children's Hospital Colorado
University of Colorado, Denver
Investigators
Principal Investigator: Jane C Burns, MD University of California, San Diego
  More Information

No publications provided

Responsible Party: Jane C. Burns, Chief, Division of Allergy, Immunology, Rheumatology, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01431105     History of Changes
Other Study ID Numbers: KD-Atorvastatin
Study First Received: September 6, 2011
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
Kawasaki disease

Additional relevant MeSH terms:
Mucocutaneous Lymph Node Syndrome
Congenital Abnormalities
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Lymphatic Diseases
Skin Diseases, Vascular
Skin Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014