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

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT01431105
• Collaborator: Children's Hospital Colorado (Other), University of Colorado, Denver (Other)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 72
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Kawasaki Disease	Drug: Atorvastatin	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atorvasatin Atorvastatin dose titration to maximum tolerated dose	Drug: Atorvastatin; Atorvastatin dose titration to maximum tolerated dose (once daily for 6 weeks); Other Names: Lipitor

Outcome Measures

Primary Outcome Measures

1. Number of Participants With SAE [At 6 weeks after initiation of study drug]

   Number of participants who experienced an SAE within the 6 week study period

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego	San Diego	California	United States	92093

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 20, 2016

More Information

Publications

None provided.

• Responsible Party: Jane C. Burns MD, Chief, Division of Allergy, Immunology, Rheumatology, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT01431105
• Other Study ID Numbers: KD-Atorvastatin
• First Posted: Sep 9, 2011
• Last Update Posted: May 6, 2020
• Last Verified: May 1, 2020

• Keywords provided by Jane C. Burns MD, Chief, Division of Allergy, Immunology, Rheumatology, University of California, San Diego: Kawasaki disease
• Additional relevant MeSH terms: Mucocutaneous Lymph Node Syndrome; Atorvastatin

Study Results

Participant Flow

Arm/Group Title	Atorvasatin
Arm/Group Description	Atorvastatin dose titration to maximum tolerated dose Atorvastatin: Atorvastatin dose titration to maximum tolerated dose (once daily for 6 weeks)
Period Title: Overall Study
STARTED	34
COMPLETED	34
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Atorvasatin
Arm/Group Description	Atorvastatin dose titration to maximum tolerated dose Atorvastatin: Atorvastatin dose titration to maximum tolerated dose (once daily for 6 weeks)
Overall Participants	34
Age (Count of Participants)
<=18 years	34 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	10 29.4%
Male	24 70.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 8.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.9%
White	21 61.8%
More than one race	8 23.5%
Unknown or Not Reported	1 2.9%
Region of Enrollment (Count of Participants)
United States	34 100%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	4

Outcome Measures

1. Primary Outcome

Title	Number of Participants With SAE
Description	Number of participants who experienced an SAE within the 6 week study period
Time Frame	At 6 weeks after initiation of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atorvasatin
Arm/Group Description	Atorvastatin treated patients
Measure Participants	34
Count of Participants [Participants]	4 11.8%

Adverse Events

Time Frame	6 weeks
Adverse Event Reporting Description	Clinicaltrials.gov definition used for AEs
Arm/Group Title	Atorvasatin
Arm/Group Description	Atorvastatin dose titration to maximum tolerated dose Atorvastatin: Atorvastatin dose titration to maximum tolerated dose (once daily for 6 weeks)
All Cause Mortality
	Atorvasatin
	Affected / at Risk (%)	# Events
Total	0/34 (0%)
Serious Adverse Events
	Atorvasatin
	Affected / at Risk (%)	# Events
Total	4/34 (11.8%)
Cardiac disorders
Worsening coronary artery aneurysm	2/34 (5.9%)	2
Immune system disorders
Recrudescent Fever	2/34 (5.9%)	2
Other (Not Including Serious) Adverse Events
	Atorvasatin
	Affected / at Risk (%)	# Events
Total	24/34 (70.6%)
Blood and lymphatic system disorders
Bruising	15/34 (44.1%)	15
Gastrointestinal disorders
Constipation or Diarrhea	5/34 (14.7%)	5
Immune system disorders
Fever	19/34 (55.9%)	19
Skin and subcutaneous tissue disorders
Viral exanthem	12/34 (35.3%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.