Erythema Chronicum Migrans
Conditions
Keywords
erythema migrans, Lyme borreliosis, doxycycline treatment, outcome, subjective symptoms
Brief summary
The purpose of this study is to compare the efficacy of 15-day versus 10-day doxycycline treatment in patients with erythema migrans.
Interventions
DRUGdoxycycline
doxycycline 100 mg bid, 10 days
DRUGplacebo
control subjects without a history of Lyme borreliosis
Sponsors
University Medical Centre Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* solitary erythema migrans in patients \> 15 years
Exclusion criteria
* a history of Lyme borreliosis in the past * pregnancy or lactation * immunocompromised status * serious adverse event to doxycycline * taking antibiotic with antiborrelial activity within 10 days * multiple erythema migrans or extracutaneous manifestations of Lyme borreliosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Sequelae and Post-treatment Subjective New or Increased Symptoms (NOIS)in Patients Treated for Erythema Migrans With Doxycycline for 10 or 15 Days. | 1 year follow-up | At each visit patients were examined and asked about the presence of any symptoms that newly developed/had worsened since erythema migrans. If such symptoms had no other medical explanation they were regarded as new or increased symptoms (NOIS). Complete response=absence of any manifestations of Lyme borreliosis, with return to pre-Lyme borreliosis health status. Partial response=presence of NOIS. Failure=presence of objective manifestations of Lyme borreliosis or persistence of B. burgdorferi sensu lato in skin at the site of the previous erythema migrans. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients (at 6 Months After Treatment With Doxycycline for 10 or 15 Days for Erythema Migrans) and Number of Control Subjects (Without a History of Lyme Borreliosis) With Nonspecific Symptoms. | 6 months after treatment | 6 months after treatment patients and controls were asked to complete a written questionnaire asking whether they had had any of 14 nonspecific symptoms (fatigue, malaise, arthralgias, headache, myalgias, pain in the spine, paresthesias, dizziness, nausea, insomnia, sleepiness, forgetfulness, concentration difficulties, or irritability) within the preceding week. For both patients and controls, the severity of each individual symptom was graded by the subject on a 10-cm visual analog scale (10 = most severe). |
Countries
Slovenia
Participant flow
Recruitment details
Patients older than 15 years evaluated between June and October 2009 at the Lyme Borreliosis Outpatient Clinic, University Medical Center Ljubljana, Slovenia were eligible for the study if they had typical solitary erythema migrans as defined by CDC. Patients were asked to refer a spouse/friend of the same age ± 5 years to serve as a control.
Pre-assignment details
241 were evaluated for enrollment and not enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| EM-10 Days Doxycycline doxycycline 100 mg b.i.d. for 10 days | 108 |
| EM-doxycycline 15 Days doxycycline 100 b.i.d. for 15 days | 117 |
| Controls subjects without a history of Lyme borreliosis included in the study at the 6 month follow-up time point | 0 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 22 | 26 | 0 |
Baseline characteristics
| Characteristic | EM-10 Days Doxycycline | EM-doxycycline 15 Days | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical >=65 years | 18 Participants | 14 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 88 Participants | 101 Participants | 189 Participants |
| Age, Continuous | 52.5 years STANDARD_DEVIATION 14.3 | 49.6 years STANDARD_DEVIATION 14 | 50.4 years STANDARD_DEVIATION 14.9 |
| Region of Enrollment Slovenia | 108 participants | 117 participants | 225 participants |
| Sex: Female, Male Female | 62 Participants | 63 Participants | 125 Participants |
| Sex: Female, Male Male | 46 Participants | 54 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 108 | 9 / 117 | 0 / 0 |
| serious Total, serious adverse events | 24 / 108 | 32 / 117 | 0 / 0 |
Outcome results
Primary
Objective Sequelae and Post-treatment Subjective New or Increased Symptoms (NOIS)in Patients Treated for Erythema Migrans With Doxycycline for 10 or 15 Days.
At each visit patients were examined and asked about the presence of any symptoms that newly developed/had worsened since erythema migrans. If such symptoms had no other medical explanation they were regarded as new or increased symptoms (NOIS). Complete response=absence of any manifestations of Lyme borreliosis, with return to pre-Lyme borreliosis health status. Partial response=presence of NOIS. Failure=presence of objective manifestations of Lyme borreliosis or persistence of B. burgdorferi sensu lato in skin at the site of the previous erythema migrans.
Time frame: 1 year follow-up
Population: Number of participants with complete response to treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EM-10 Days Doxycycline | Objective Sequelae and Post-treatment Subjective New or Increased Symptoms (NOIS)in Patients Treated for Erythema Migrans With Doxycycline for 10 or 15 Days. | number of patients with NOIS | 7 number of participants |
| EM-10 Days Doxycycline | Objective Sequelae and Post-treatment Subjective New or Increased Symptoms (NOIS)in Patients Treated for Erythema Migrans With Doxycycline for 10 or 15 Days. | number of patients with complete response | 79 number of participants |
| EM-doxycycline 15 Days | Objective Sequelae and Post-treatment Subjective New or Increased Symptoms (NOIS)in Patients Treated for Erythema Migrans With Doxycycline for 10 or 15 Days. | number of patients with NOIS | 6 number of participants |
| EM-doxycycline 15 Days | Objective Sequelae and Post-treatment Subjective New or Increased Symptoms (NOIS)in Patients Treated for Erythema Migrans With Doxycycline for 10 or 15 Days. | number of patients with complete response | 85 number of participants |
| Controls | Objective Sequelae and Post-treatment Subjective New or Increased Symptoms (NOIS)in Patients Treated for Erythema Migrans With Doxycycline for 10 or 15 Days. | number of patients with complete response | 81 number of participants |
| Controls | Objective Sequelae and Post-treatment Subjective New or Increased Symptoms (NOIS)in Patients Treated for Erythema Migrans With Doxycycline for 10 or 15 Days. | number of patients with NOIS | NA number of participants |
Secondary
Number of Patients (at 6 Months After Treatment With Doxycycline for 10 or 15 Days for Erythema Migrans) and Number of Control Subjects (Without a History of Lyme Borreliosis) With Nonspecific Symptoms.
6 months after treatment patients and controls were asked to complete a written questionnaire asking whether they had had any of 14 nonspecific symptoms (fatigue, malaise, arthralgias, headache, myalgias, pain in the spine, paresthesias, dizziness, nausea, insomnia, sleepiness, forgetfulness, concentration difficulties, or irritability) within the preceding week. For both patients and controls, the severity of each individual symptom was graded by the subject on a 10-cm visual analog scale (10 = most severe).
Time frame: 6 months after treatment
Population: number of participants with nonspecific symptoms
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EM-10 Days Doxycycline | Number of Patients (at 6 Months After Treatment With Doxycycline for 10 or 15 Days for Erythema Migrans) and Number of Control Subjects (Without a History of Lyme Borreliosis) With Nonspecific Symptoms. | 151 number of participants |
| EM-doxycycline 15 Days | Number of Patients (at 6 Months After Treatment With Doxycycline for 10 or 15 Days for Erythema Migrans) and Number of Control Subjects (Without a History of Lyme Borreliosis) With Nonspecific Symptoms. | 60 number of participants |