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

This study has been completed.
Sponsor:
Collaborator:
Slovenian Research Agency
Information provided by (Responsible Party):
Franc Strle, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier:
NCT01518192
First received: June 28, 2010
Last updated: December 18, 2011
Last verified: December 2011
  Purpose

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.

Condition Intervention Phase
Erythema Migrans
Post-Lyme Disease Symptoms
Drug: doxycycline
Drug: cefuroxime axetil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by University Medical Centre Ljubljana:

Primary Outcome Measures:
  • Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days [ Time Frame: at 14 days post inclusion ] [ Designated as safety issue: No ]
    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

  • Adverse Events [ Time Frame: at 14 days ] [ Designated as safety issue: Yes ]
    Number of patients reporting adverse events

  • Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    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

  • Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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

  • Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Comparison of the number patients and controls with new or increased symptoms since erythema migrans at 6 months.

  • New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Comparison of the number of patients and controls with new or increased symptoms since erythema migrans at 12 months.

  • Selected Subjective Symptoms in Patients and Control Subjects [ Time Frame: Examination at 12 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 544
Study Start Date: June 2006
Study Completion Date: January 2009
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1Doxycycline Drug: doxycycline
100 mg bid; 15 days
Active Comparator: 2 Cefuroxime axetil Drug: cefuroxime axetil
500 mg bid; 15 days

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

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01518192

Locations
Slovenia
Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
Ljubljana, Slovenia, 1525
Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana
Ljubljana, Slovenia, 1000
Sponsors and Collaborators
University Medical Centre Ljubljana
Slovenian Research Agency
Investigators
Principal Investigator: Daša Cerar, MD Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
Study Chair: Franc Strle, MD Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
  More Information

No publications provided

Responsible Party: Franc Strle, M.D., PhD, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier: NCT01518192     History of Changes
Other Study ID Numbers: EM-DC
Study First Received: June 28, 2010
Results First Received: June 28, 2010
Last Updated: December 18, 2011
Health Authority: Slovenia: Ethics Committee

Keywords provided by University Medical Centre Ljubljana:
erythema migrans
doxycycline
cefuroxime axetil
post-Lyme disease symptoms
background symptoms in general population

Additional relevant MeSH terms:
Erythema Chronicum Migrans
Glossitis, Benign Migratory
Lyme Disease
Erythema
Borrelia Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Tick-Borne Diseases
Skin Diseases, Bacterial
Spirochaetales Infections
Skin Diseases, Infectious
Infection
Skin Diseases
Glossitis
Tongue Diseases
Mouth Diseases
Stomatognathic Diseases
Cefuroxime
Cefuroxime axetil
Doxycycline
Doxycycline hyclate
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on April 22, 2014