Comparing 3 Antibiotic Regimes for Erythema Migrans in General Practice

Study Overview
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Brief Summary
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Tick borne diseases are increasing in Norway. Lyme borreliosis is the most common infection. Erythema migrans is mainly diagnosed and treated in general practice. There is disagreement about what antibiotic treatment that should be given. An RCT with the three most common antibiotics used, will support data for revision of national guidelines.

Detailed Description
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Comparison of phenoxymethylpenicillin, doxycycline and amoxicillin for Erythema migrans in Norwegian general practice. Every patient receives 14 days of antibiotic treatment. There are blood samples for measurement of Borrelia antibody level at day 1, 14 and 90 and questionnaires on subjective health complaints (SHC) at day 1, 90 and 360. Side symptoms and side effects are registered. For volunteers there is an additional PCR-analysis on punch biopsy from the EM for subgrouping of the Borrelia bacteria. TBE-antibodies are measured on day 14. Antibody levels and SHC-scores are compared to healthy blood donors.

Official Title
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Tick Borne Diseases in Norwegian General Practice. A Randomized, Controlled Trial for Treatment of Erythema Migrans in Norwegian General Practice. A Comparison of Phenoxymethylpenicillin, Amoxicillin and Doxycycline.

Conditions
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Erythema Migrans, Erythema Chronicum Migrans, Borreliosis, Lyme Disease, Early Lyme Disease

Intervention / Treatment
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* Drug: Doxycycline
* Drug: Phenoxymethylpenicillin
* Drug: Amoxicillin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Erythema migrans Over the age of 18 Signing an concent form after information in writing Exclusion Criteria: Allergic to any of the three drugs in the study Under the age of 18 Pregnancy Dementia or known drug abuse Antibiotic treatment last 14 days Concommitant Chemotherapy or immunomodulating therapy Concommitant use of medicine with potential interaction (defined in protocol)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Doxycycline<br>Doxycycline, 100 mg, tablets, b.i.d., 14 days | Drug: Doxycycline<br>* 1 tablet, 100 mg, b.i.d. 14 days<br>* Other names: Doksycycline 100 mg HEXAL, no. 30;|
| Active Comparator: Penicillin<br>Phenoxymethylpenicillin tablets 650 mg. 2 tablets t.i.d. 14 days | Drug: Phenoxymethylpenicillin<br>* Tablet 650 mg, 2 tablets, t.i.d., 14 days<br>* Other names: Weifapenin 650 mg, WEIFA, no. 100;|
| Active Comparator: Amoxicillin<br>Amoxicillin 500 mg capsula, t.i.d., 14 days | Drug: Amoxicillin<br>* Capsula, 500 mg, t.i.d., 14 days<br>* Other names: Amoxicillin 500 mg MYLAN, no. 30 + 20.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Erythema migrans (EM) | On day 1 duration until first the consulation is registered. Day 1-14 the EM is registered in a patient diary. On day 14 the doctor is asked whether the EM has disseapeared. If not the patient is followed by phone from the researchers. On day 90 they are additionally asked for how long it lasted. | 1-90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Health Complaints (SHC) | By questionnaire on day 1, day 90 and day 360 the patients are asked about their SHC which is a standardized set of parametres. The 3 treatment groups are compaired to each other and to 1200 healthy blood donors receiving the same questionnaire. There are 29 standardized and 3 Lyme disease related subjects to be measured. | 1 year | 
| Borrelia antibodies | Normally antibody production is not measured for EM as it is a clinical diagnosis, and less than 50 percent of EM-patients are expected to develop antibodies in the first period. However antibodies are here measured on day 1, day 14 and day 90 to see whether there are differences between the groups. Also the results will be compared to the blood donors. | 1-90 days | 
| Side symptoms | The EM in it self is often asymptomatic, and fever, headache and nerval palsy can be a sign of disseminated disease or co-infection. On the quiestionnaire to the pasient and doctor on day 1, in the patient diary day 1-14 and on the questionnaire to the doctor on day 14 these side symptoms are registered. In a potential case, where it turns out that the patient suffers from disseminated disease this will be regostered as treatment failure in the study and the patient treated and/or referred as normal. | 1-14 days | 
| Side effects | The antibiotic tretments are expected to be non-inferior to each other. Potensial side effects as nausea, diarrhea etc. are registered in the patients diary day 1-14 and in the doctors quiestionnaire on day 14. | 1-14 days | 
| Subgrouping and TBE | For volunteers there is an additional PCR-analysis on punch biopsy from the EM for subgroupring of the Borrelia bacteria. TBE-antibodies are measured on day 14. | 1-14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotics, General Practice, Erythema migrans, Borrelia, Ticks