Comparison of Doxycycline and Cefuroxime Axetil for Treatment of Erythema Migrans: Clinical and Microbiological Outcome

Erythema Migrans Clinical Trial

Official title:

Risk Factors for Failure of Erythema Migrans Treatment - Comparison of Doxycycline and Cefuroxime Axetil for Treatment of Adult Patients With Erythema Migrans: Clinical and Microbiological Outcome.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01518192
• Other study ID #: EM-DC
• Status: Completed
• Phase: Phase 4
• First received: June 28, 2010
• Last updated: December 18, 2011
• Start date: June 2006
• Est. completion date: January 2009

Study information

• Verified date: December 2011
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Health authority: Slovenia: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Background:

• While doxycycline is a standard antibiotic for treatment of erythema migrans in Europe as well as in the USA, the effectiveness of cefuroxime axetil in the treatment of adult patients with erythema migrans has been assessed only in the USA where the causative agent of Lyme disease is Borrelia burgdorferi, but not in Europe where the main etiologic agents are B. afzelii and B. garinii.

• Controversy exists over the significance and even the existence of post-Lyme disease symptoms because of the high rate of similar background symptoms in the general population.

Purpose:

The two main purposes of this European, prospective clinical trial in which doxycycline and cefuroxime axetil are compared in the treatment of adult patients with erythema migrans and which included a control group to address the significance of post-Lyme disease symptoms are:

• To assess and compare the effectiveness of doxycycline and cefuroxime axetil in the treatment of erythema migrans using clinical and bacteriological criteria (noninferiority testing approach), and

• to compare the frequency of post-Lyme disease symptoms in adult patients treated for EM with antibiotics and the frequency of similar symptoms in control subjects without Lyme disease.

Description:

Sample size

Decisions were based on the following:

1. Number of patients with erythema migrans treated with doxycycline and cefuroxime axetil was determined assuming no difference in treatment outcome will be detected (non-inferiority testing).

2. The decision for a larger sample sizes than needed for 1. was done with the intention to evaluate the secondary outcome measure, i.e., to assess the difference between the frequency of new or increased symptoms in patients treated for early Lyme disease and the occurrence of the same symptoms in control subjects.

1. We assumed that the outcomes in the two treatment groups will be comparable and that the patients could be combined for further analysis.

2. To obtain a control group from the same geographical area, each patient was asked if she or he had a family member or friend who was within 5 years of her or his age and who was without a history of Lyme borreliosis. These persons were approached by a short written explanation of the investigation, containing also a request for their participation. We assumed that we will be able to get a corresponding control person not for all but for approximately 80-90% of patients.

3. Under the assumption that approximately 15% of an estimated 200 patients would have new or increased symptoms at >6 months after enrollment into the study, a control group of 165 subjects would be sufficient to detect a >10 percentage point lower rate of new or increased symptoms in controls compared with patients at the 0.05 level (2-sided) with >90% power. To comply with drop outs at different time points we assessed that 280 patients and 230 controls should be included at baseline.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 544
• Est. completion date: January 2009
• Est. primary completion date: November 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• patients 15 or more years old

• with typical erythema migrans

• evaluated between 6/06 and 9/06

• evaluated at the Lyme Disease Outpatient Clinic, University Medical Center Ljubljana, Slovenia.

Exclusion Criteria:

• history of Lyme disease in the past

• pregnancy

• lactation

• immunocompromising condition

• history of a serious adverse reaction to a beta-lactam or tetracycline drug

• receiving an antibiotic with known anti-borrelial activity within 10 days

• multiple erythema migrans lesions or an extracutaneous manifestation of Lyme disease.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Erythema
• Erythema Chronicum Migrans
• Erythema Migrans
• Lyme Disease
• Post-Lyme Disease Symptoms

Intervention

Drug:
• doxycycline
100 mg bid; 15 days
• cefuroxime axetil
500 mg bid; 15 days

Locations

Country	Name	City	State
Slovenia	Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia	Ljubljana
Slovenia	Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana	Ljubljana

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana	Slovenian Research Agency

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days	Number of patients with objective manifestations of Lyme disease(persistence of erythema migrans or any of the extracutaneous-cardiac, nervous or skeletal-Lyme disease manifestations)and/or with post-Lyme disease symptoms in patients treated for solitary erythema migrans at 14 days post inclusion	at 14 days post inclusion	No
Primary	Adverse Events	Number of patients reporting adverse events	at 14 days	Yes
Primary	Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months	Number of patients with objective Lyme disease manifestations and/or post-Lyme disease symptoms in patients treated for solitary erythema migrans at 2 months post inclusion	2 months	No
Primary	Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months	Number of patients with objective Lyme disease manifestations and/or post-Lyme disease symptoms in patients treated for solitary erythema migrans at 6 months post inclusion	6 months	No
Primary	Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months	Number of patients with objective Lyme disease manifestations and/or post-Lyme disease symptoms in patients treated for solitary erythema migrans at 12 months post inclusion	12 months	No
Secondary	New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.	Comparison of the number patients and controls with new or increased symptoms since erythema migrans at 6 months.	6 months	No
Secondary	New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.	Comparison of the number of patients and controls with new or increased symptoms since erythema migrans at 12 months.	12 months	No
Secondary	Selected Subjective Symptoms in Patients and Control Subjects	Comparison of the number of patients and controls with selected 8 symptoms (fatigue, arthralgias, myalgias, headache, paresthesias, dizziness, irritability, or nausea) within the preceding week, irrespective of whether they were new or increased since erythema migrans.	Examination at 12 months	No