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

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ClinicalTrials.gov Identifier: NCT01518192
Recruitment Status : Completed
First Posted : January 25, 2012
Results First Posted : January 25, 2012
Last Update Posted : January 25, 2012
Sponsor:
Collaborator:
Slovenian Research Agency
Information provided by (Responsible Party):
Franc Strle, University Medical Centre Ljubljana

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Erythema Migrans
Post-Lyme Disease Symptoms
Interventions: Drug: doxycycline
Drug: cefuroxime axetil

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

113/398 patients were ineligible due to:

  • receiving antibiotic with known anti-borrelial activity (73)
  • multiple erythema migrans (16)
  • history of Lyme disease (12)
  • immunocompromising condition (4)
  • serious adverse reaction to study drugs (3)
  • pregnancy or lactation (4)
  • erythema migrans accompanied by meningitis (1)

Reporting Groups
  Description
Doxycycline

Patients were assigned to receive a 15-day oral treatment with doxycycline 100 mg twice daily.

At baseline and at 14 days, 2, 6, and 12 months thereafter, patients were interviewed and examined. At baseline, a skin biopsy specimen was cultured; this procedure was repeated 2-3 months later in patients with a positive culture.

Cefuroxime Axetil

Patients were assigned to receive a 15-day oral treatment with cefuroxime axetil 500 mg twice daily.

At baseline and at 14 days, 2, 6, and 12 months thereafter, patients were interviewed and examined. At baseline, a skin biopsy specimen was cultured; this procedure was repeated 2-3 months later in patients with a positive culture.

Controls patients' family members or friends without a history of Lyme disease

Participant Flow:   Overall Study
    Doxycycline   Cefuroxime Axetil   Controls
STARTED   145   140   259 
COMPLETED   116   114   224 
NOT COMPLETED   29   26   35 
Lost to Follow-up                29                26                35 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Doxycycline

Patients were assigned to receive a 15-day oral treatment with either doxycycline 100 mg or cefuroxime axetil 500 mg twice daily, by alternating treatment regimens each week.

Evaluations:

At baseline and at 14 days, 2, 6, and 12 months thereafter, patients were interviewed and examined. At baseline, a skin biopsy specimen was cultured as previously described; this procedure was repeated 2-3 months later in patients with a positive culture.

Cefuroxime Axetil

Patients were assigned to receive a 15-day oral treatment with either doxycycline 100 mg or cefuroxime axetil 500 mg twice daily, by alternating treatment regimens each week.

Evaluations:

At baseline and at 14 days, 2, 6, and 12 months thereafter, patients were interviewed and examined. At baseline, a skin biopsy specimen was cultured as previously described; this procedure was repeated 2-3 months later in patients with a positive culture.

Controls To obtain a control group from the same geographical area, each patient was asked if he/she had a family member or friend who was within 5 years of his/her age and had no history of Lyme disease (two of the potential control subjects were excluded due to this reason), and was not pregnant, lactating or immunocompromised.
Total Total of all reporting groups

Baseline Measures
   Doxycycline   Cefuroxime Axetil   Controls   Total 
Overall Participants Analyzed 
[Units: Participants]
 145   140   259   544 
Age 
[Units: Years]
Median (Full Range)
 54 
 (17 to 85) 
 51.5 
 (19 to 82) 
 52 
 (15 to 85) 
 52.5 
 (15 to 85) 
Gender 
[Units: Participants]
       
Female   84   77   125   286 
Male   61   63   134   258 
Region of Enrollment 
[Units: Participants]
       
Slovenia   145   140   259   544 


  Outcome Measures

1.  Primary:   Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days   [ Time Frame: at 14 days post inclusion ]

Measure Type Primary
Measure Title Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days
Measure Description 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who followed the protocol were eligible for analysis

Reporting Groups
  Description
Doxycycline doxycycline 100 mg twice daily for 15 days
Cefuroxime Axetil cefuroxime axetil 500 mg twice daily for 15 days

Measured Values
   Doxycycline   Cefuroxime Axetil 
Participants Analyzed   145   140 
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days 
[Units: Participants]
 30   27 

No statistical analysis provided for Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days



2.  Primary:   Adverse Events   [ Time Frame: at 14 days ]

Measure Type Primary
Measure Title Adverse Events
Measure Description Number of patients reporting adverse events
Time Frame at 14 days  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who followed the protocol.

Reporting Groups
  Description
Doxycycline doxycycline 100 mg twice daily for 15 days
Cefuroxime Axetil cefuroxime axetil 500 mg twice daily for 15 days

Measured Values
   Doxycycline   Cefuroxime Axetil 
Participants Analyzed   145   140 
Adverse Events 
[Units: Participants]
 22   23 

No statistical analysis provided for Adverse Events



3.  Primary:   Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months   [ Time Frame: 2 months ]

Measure Type Primary
Measure Title Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months
Measure Description 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all participants who followed the protocol

Reporting Groups
  Description
Doxycycline doxycycline 100 mg twice daily for 15 days
Cefuroxime Axetil cefuroxime axetil 500 mg twice daily for 15 days

Measured Values
   Doxycycline   Cefuroxime Axetil 
Participants Analyzed   136   134 
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months 
[Units: Participants]
 19   14 

No statistical analysis provided for Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months



4.  Primary:   Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months   [ Time Frame: 6 months ]

Measure Type Primary
Measure Title Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months
Measure Description 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all participants who followed the protocol

Reporting Groups
  Description
Doxycycline doxycycline 100 mg twice daily for 15 days
Cefuroximew Axetil cefuroxime axetil 500 mg twice daily for 15 days

Measured Values
   Doxycycline   Cefuroximew Axetil 
Participants Analyzed   102   93 
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months 
[Units: Participants]
 5   6 

No statistical analysis provided for Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 6months



5.  Primary:   Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months   [ Time Frame: 12 months ]

Measure Type Primary
Measure Title Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months
Measure Description 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all participants who followed the protocol

Reporting Groups
  Description
Doxycycline doxycycline 100 mg twice daily for 15 days
Cefuroxime Axetil cefuroxime axetil 500 mg twice daily for 15 days

Measured Values
   Doxycycline   Cefuroxime Axetil 
Participants Analyzed   116   114 
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months 
[Units: Participants]
 3   4 

No statistical analysis provided for Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 12 Months



6.  Secondary:   New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.
Measure Description Comparison of the number patients and controls with new or increased symptoms since erythema migrans at 6 months.
Time Frame 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all participants who followed the protocol

Reporting Groups
  Description
Patients patients with new or increased symptoms since erythema migrans at 6 months post inclusion
Controls controls with new or increased symptoms since enrollment at 6 months post inclusion

Measured Values
   Patients   Controls 
Participants Analyzed   194   236 
New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months. 
[Units: Participants]
 9   16 

No statistical analysis provided for New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.



7.  Secondary:   New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.   [ Time Frame: 12 months ]

Measure Type Secondary
Measure Title New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.
Measure Description Comparison of the number of patients and controls with new or increased symptoms since erythema migrans at 12 months.
Time Frame 12 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all participants who followed the protocol

Reporting Groups
  Description
Patients patients with new or increased symptoms since erythema migrans at 12 months post inclusion
Controls controls with new or increased symptoms since erythema migrans at 12 months post inclusion

Measured Values
   Patients   Controls 
Participants Analyzed   230   224 
New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months. 
[Units: Participants]
 5   21 

No statistical analysis provided for New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.



8.  Secondary:   Selected Subjective Symptoms in Patients and Control Subjects   [ Time Frame: Examination at 12 months ]

Measure Type Secondary
Measure Title Selected Subjective Symptoms in Patients and Control Subjects
Measure Description 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all participants who followed the protocol

Reporting Groups
  Description
Patients patients with selected subjective symptoms at 12 months post inclusion
Controls controls with selected subjective symptoms at 12 months post inclusion

Measured Values
   Patients   Controls 
Participants Analyzed   230   224 
Selected Subjective Symptoms in Patients and Control Subjects 
[Units: Participants]
 178   181 

No statistical analysis provided for Selected Subjective Symptoms in Patients and Control Subjects




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information

Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Franc Strle
Organization: Department of Infectious Diseases, University Medical Center Ljubljana
phone: +386 1 522 2610
e-mail: franc.strle@kclj.si



Responsible Party: Franc Strle, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier: NCT01518192     History of Changes
Other Study ID Numbers: EM-DC
First Submitted: June 28, 2010
First Posted: January 25, 2012
Results First Submitted: June 28, 2010
Results First Posted: January 25, 2012
Last Update Posted: January 25, 2012