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.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 544
- 试验地点
- 2
- 主要终点
- Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
2 Cefuroxime axetil
干预措施: cefuroxime axetil (Drug)
1Doxycycline
干预措施: doxycycline (Drug)
结局指标
主要结局
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 14 Days
时间窗: 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
时间窗: at 14 days
Number of patients reporting adverse events
Objective Lyme Disease Manifestations and Post-Lyme Disease Symptoms at 2 Months
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- New or Increased Symptoms Since Erythema Migrans in Patients and Controls at 6 Months.(6 months)
- New or Increased Symptoms Since Erythema Migrans in Patients Controls at 12 Months.(12 months)
- Selected Subjective Symptoms in Patients and Control Subjects(Examination at 12 months)
研究者
Franc Strle
M.D., PhD
University Medical Centre Ljubljana