Clinical trial NCT01518192: Comparison of Doxycycline and Cefuroxime Axetil for Treatment of Erythema Migrans: Clinical and Microbiological Outcome
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Erythema Migrans
Post-Lyme Disease Symptoms
Keywords: erythema migrans
doxycycline
cefuroxime axetil
post-Lyme disease symptoms
background symptoms in general population
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: Slovenian Research Agency
First posted: 2012-01-25
Enrollment: 544
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days
timeFrame: at 14 days post inclusion
measure: Adverse Events
timeFrame: at 14 days
measure: Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months
timeFrame: 2 months
measure: Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months
timeFrame: 6 months
measure: Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months
timeFrame: 12 months
Secondary outcomes:
measure: New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.
timeFrame: 6 months
measure: New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.
timeFrame: 12 months
measure: Selected Subjective Symptoms in Patients and Control Subjects
timeFrame: Examination at 12 months
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana
city: Ljubljana
country: Slovenia
facility: Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
Study officials:
affiliation: Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
name: Daša Cerar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
name: Franc Strle, MD
role: STUDY_CHAIR
References: