Erythema MigransPhase 4NCT01518192
Comparison of Doxycycline and Cefuroxime Axetil for Treatment of Erythema Migrans: Clinical and Microbiological Outcome
A Phase 4 study testing doxycycline and cefuroxime axetil in people with Erythema Migrans and Post-Lyme Disease Symptoms, run by University Medical Centre Ljubljana at 2 sites in Slovenia.
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… Read more about this study
- Who is it for?
- Ages 15 years and olderHealthy volunteers can take part
- Conditions the study is for
- Erythema Migrans, Post-Lyme Disease Symptoms
- What is being tested?
- doxycycline and cefuroxime axetil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 544 participants
- Where
- 2 sitesSlovenia
- Study dates
- Jun 2006to Jan 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Slovenia2 sites
Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana
Ljubljana, 1000
Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
Ljubljana, 1525
About this study
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.
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.
Read more
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.
- We assumed that the outcomes in the two treatment groups will be comparable and that the patients could be combined for further analysis.
- 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.
- 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
- Erythema Migrans, Post-Lyme Disease Symptoms
- Being tested
- doxycycline, cefuroxime axetil
- Keywords
- erythema migrans, doxycycline, cefuroxime axetil, post-Lyme disease symptoms, background symptoms in general population
- Medical subject headings
- Glossitis, Benign Migratory
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxycyclineDrug
100 mg bid; 15 days
cefuroxime axetilDrug
500 mg bid; 15 days
| Study group | Role | What they receive |
|---|---|---|
| 1Doxycycline | Active comparator | Not described Receives: Drug: doxycycline |
| 2 Cefuroxime axetil | Active comparator | Not described Receives: Drug: cefuroxime axetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at 14 days post inclusion
Adverse Events
Number of patients reporting adverse events
Measured: 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
Measured: 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
Measured: 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
Measured: 12 months
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Examination at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startJun 2006
- Primary completionNov 2007
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Erythema MigransStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 544 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- Slovenian Research Agency
- Responsible party
- Principal investigator, Franc Strle, University Medical Centre Ljubljana
- Investigators
- Daša Cerar, MD, Principal investigator, Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, SloveniaFranc Strle, MD, Study chair, Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01518192
- Sponsor's protocol ID
- EM-DC
- Status last verified
- Dec 2011
- First submitted
- 28 Jun 2010
- Last updated
- 25 Jan 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01518192
- Acronym / sponsor ID
- EM-DC
- Conditions
- Erythema Migrans, Post-Lyme Disease Symptoms
- Keywords
- erythema migrans, doxycycline, cefuroxime axetil, post-Lyme disease symptoms, background symptoms in general population
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 544 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Collaborators
- Slovenian Research Agency
- Study start
- Jun 2006
- Primary completion
- Nov 2007 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 25 Jan 2012 (estimated)
- Results
- Posted 25 Jan 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- We assumed that the outcomes in the two treatment groups will be comparable and that the patients could be combined for further analysis.
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1Doxycycline | Active comparator | Drug: doxycycline |
| 2 Cefuroxime axetil | Active comparator | Drug: cefuroxime axetil |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- history of Lyme disease in the past
- pregnancy
- lactation
- immunocompromising condition
- history of a serious adverse reaction to a beta-lactam or tetracycline drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxycycline100 mg bid; 15 days | Drug | 1Doxycycline |
| cefuroxime axetil500 mg bid; 15 days | Drug | 2 Cefuroxime axetil |
Primary outcome
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days
Time frame: at 14 days post inclusion
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
Number of patients reporting adverse events
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months
Time frame: 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
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months
Time frame: 6 months
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
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
3 secondary outcomes
New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.
Time frame: 6 months
New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.
Time frame: 12 months
Selected Subjective Symptoms in Patients and Control Subjects
Time frame: Examination at 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing doxycycline and cefuroxime axetil in people with Erythema Migrans and Post-Lyme Disease Symptoms, run by University Medical Centre Ljubljana at 2 sites in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jan 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days (time frame: at 14 days post inclusion). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2012; AzTrials last refreshed its copy on 8 Nov 2026.