Comparing 3 Antibiotic Regimes for Erythema Migrans in General Practice (NorTick_EM)

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.

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.

Study Overview

• Status: Completed
• Conditions: Lyme Disease; Erythema Migrans; Erythema Chronicum Migrans; Borreliosis; Early Lyme Disease
• Intervention / Treatment: Drug: Doxycycline; Drug: Phenoxymethylpenicillin; Drug: Amoxicillin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 225
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0318
    • Antibiotic Centre for Primary Care, University of Oslo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Morten Lindbaek
• Collaborators: Norwegian Institute of Public Health; Sorlandet Hospital HF; Norwegian University of Life Sciences
• Investigators: Principal Investigator: Morten Lindbak, Professor, University of Oslo

Publications and helpful links

General Publications

• Eliassen KE, Reiso H, Berild D, Lindbaek M. Comparison of phenoxymethylpenicillin, amoxicillin, and doxycycline for erythema migrans in general practice. A randomized controlled trial with a 1-year follow-up. Clin Microbiol Infect. 2018 Dec;24(12):1290-1296. doi: 10.1016/j.cmi.2018.02.028. Epub 2018 Mar 2.

Helpful Links

• Information from the Antibiotic Centre for Primary Care

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 6, 2011
• First Submitted That Met QC Criteria: June 6, 2011
• First Posted (Estimate): June 7, 2011

Study Record Updates

• Last Update Posted (Estimate): December 12, 2014
• Last Update Submitted That Met QC Criteria: December 11, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Antibiotics; General Practice; Borrelia; Erythema migrans; Ticks
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Stomatognathic Diseases; Mouth Diseases; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Skin Manifestations; Skin Diseases, Bacterial; Tick-Borne Diseases; Borrelia Infections; Spirochaetales Infections; Tongue Diseases; Glossitis; Erythema; Lyme Disease; Erythema Chronicum Migrans; Glossitis, Benign Migratory; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline; Amoxicillin; Penicillin V
• Other Study ID Numbers: EUDRACT 2010-023747