CompletedNCT01518192Updated Jan 25, 2012Results posted

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

A Phase 4 interventional study of doxycycline and cefuroxime axetil in Erythema Migrans and Post-Lyme Disease Symptoms, sponsored by University Medical Centre Ljubljana. Completed at 2 sites in Slovenia. Open to participants aged 15 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2012-01-25.

Sponsored by University Medical Centre Ljubljana · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 544
Allocation: Randomized
Ages: 15 Years and older
Sex: All

Study 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.

Read the detailed description

Sample size

Decisions were based on the following:

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).
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.

Conditions studied

Erythema Migrans
Post-Lyme Disease Symptoms

Browse trials for

Glossitis, Benign Migratory 25

Keywords

erythema migrans
doxycycline
cefuroxime axetil
post-Lyme disease symptoms
background symptoms in general population

In context

Glossitis, Benign Migratory

25 studies on the registry are indexed under Glossitis, Benign Migratory; 4 are open to participants now.

This study's enrollment of 544 is above the median of 200 across 13 interventional studies indexed under Glossitis, Benign Migratory.

Browse Glossitis, Benign Migratory studies →

Lead sponsor

University Medical Centre Ljubljana is the lead sponsor of 296 studies on the registry; 72 are open to participants now.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 15 Years and older
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 544 participants (actual)

Study arms

Active comparator
1Doxycycline
Drug: doxycycline
Active comparator
2 Cefuroxime axetil
Drug: cefuroxime axetil

Interventions

Drugdoxycycline
100 mg bid; 15 days
Drugcefuroxime axetil
500 mg bid; 15 days

What researchers measure

Primary outcomes

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
Time frame: at 14 days post inclusion
Adverse Events
Number of patients reporting adverse events
Time frame: at 14 days
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
Time frame: 2 months
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
Time frame: 6 months
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
Time frame: 12 months

Secondary outcomes

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.
Time frame: 6 months
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.
Time frame: 12 months
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.
Time frame: Examination at 12 months

Results

Posted Jan 25, 2012

Limitations and caveats

Medical explanation besides Lyme disease of the symptoms in patients was based on history and physical examination, therefore some other medical explanations might have been missed. With regard to controls this was even more likely.

Participant flow

Adult patients with typical erythema migrans, examined in the period from June to September 2006 at Lyme Disease Outpatient Clinic, University Medical Center Ljubljana, Slovenia

Participant flow — Overall Study
Milestone	Doxycycline	Cefuroxime Axetil	Controls
Started	145	140	259
Completed	116	114	224
Not completed	29	26	35
Withdrew: Lost to follow-up	29	26	35

Outcome measures

PrimaryObjective 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

Time frame:: at 14 days post inclusion
Reported as:: Number · participants

Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days
participants	Doxycycline	Cefuroxime Axetil
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days	30	27

SecondaryNew 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.

Time frame:: 6 months
Reported as:: Number · participants

New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.
participants	Patients	Controls
New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.	9	16

PrimaryAdverse Events

Number of patients reporting adverse events

Time frame:: at 14 days
Reported as:: Number · participants

Adverse Events
participants	Doxycycline	Cefuroxime Axetil
Adverse Events	22	23

PrimaryObjective 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

Time frame:: 2 months
Reported as:: Number · participants

Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months
participants	Doxycycline	Cefuroxime Axetil
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months	19	14

PrimaryObjective 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

Time frame:: 6 months
Reported as:: Number · participants

Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months
participants	Doxycycline	Cefuroximew Axetil
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months	5	6

PrimaryObjective 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

Time frame:: 12 months
Reported as:: Number · participants

Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months
participants	Doxycycline	Cefuroxime Axetil
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months	3	4

SecondaryNew 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.

Time frame:: 12 months
Reported as:: Number · participants

New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.
participants	Patients	Controls
New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.	5	21

SecondarySelected 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.

Time frame:: Examination at 12 months
Reported as:: Number · participants

Selected Subjective Symptoms in Patients and Control Subjects
participants	Patients	Controls
Selected Subjective Symptoms in Patients and Control Subjects	178	181

Adverse events

Collected over 2 months. Non-serious events are listed at a 0.7% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Doxycycline	—	0/145 (0%)	21/145 (14.5%)
Cefuroxime Axetil	—	0/140 (0%)	21/140 (15%)
Controls	—	0/259 (0%)	0/259 (0%)

Most frequent other events

Most frequent other events
Event	Doxycycline	Cefuroxime Axetil	Controls
Gastrointestinal symptomsGastrointestinal disorders	20/145	21/140	0/259
PhotosensitivityGeneral disorders	1/145	0/140	0/259

Baseline characteristics

Age Continuous
Age Continuous(years)	Doxycycline	Cefuroxime Axetil	Controls	Total
Median	54 ± 14.6	51.5 ± 14.9	52 (15 to 85)	52.5 ± 14.9

Sex: Female, Male
Sex: Female, Male(Participants)	Doxycycline	Cefuroxime Axetil	Controls	Total
Female	84	77	125	286.0
Male	61	63	134	258.0

Region of Enrollment
Region of Enrollment(participants)	Doxycycline	Cefuroxime Axetil	Controls	Total
Slovenia	145	140	259	544.0

Study locations

2 sites

Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana
Ljubljana, 1000, Slovenia
Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
Ljubljana, 1525, Slovenia

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 25, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01518192
Lead sponsor: University Medical Centre Ljubljana
Collaborators: Slovenian Research Agency
Responsible party: Franc Strle (M.D., PhD, University Medical Centre Ljubljana) — Principal investigator
First posted: Jan 25, 2012
Start date: Jun 2006
Primary completion: Nov 2007
Completion: Jan 2009
Results posted: Jan 25, 2012
Last update: Jan 25, 2012

Study contacts

Daša Cerar, MD

principal investigator · Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia

Franc Strle, MD

study chair · Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Doxycycline · Cefuroxime axetil

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