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

• ClinicalTrials.gov Identifier: NCT01368341
• Recruitment Status: Completed
• First Posted: June 7, 2011
• Last Update Posted: December 12, 2014
• Sponsor: Morten Lindbaek
• Collaborators: Norwegian Institute of Public Health; Sorlandet Hospital HF; Norwegian University of Life Sciences
• Information provided by (Responsible Party): Morten Lindbaek, University of Oslo

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Erythema Migrans; Erythema Chronicum Migrans; Borreliosis; Lyme Disease; Early Lyme Disease	Drug: Doxycycline; Drug: Phenoxymethylpenicillin; Drug: Amoxicillin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 225 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: June 2011
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2014

Arms and Interventions

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 Name: 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 Name: 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 Name: Amoxicillin 500 mg MYLAN, no. 30 + 20.

Outcome Measures

Primary Outcome Measures :

1. Duration of Erythema migrans (EM) [ Time Frame: 1-90 days ]
   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.

Secondary Outcome Measures :

1. Subjective Health Complaints (SHC) [ Time Frame: 1 year ]
   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.
2. Borrelia antibodies [ Time Frame: 1-90 days ]
   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.
3. Side symptoms [ Time Frame: 1-14 days ]

   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.

4. Side effects [ Time Frame: 1-14 days ]
   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.
5. Subgrouping and TBE [ Time Frame: 1-14 days ]
   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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

Norway

Antibiotic Centre for Primary Care, University of Oslo

Oslo, Norway, 0318

Sponsors and Collaborators

Morten Lindbaek

Norwegian Institute of Public Health

Sorlandet Hospital HF

Norwegian University of Life Sciences

Investigators

• Principal Investigator: Morten Lindbak, Professor; University of Oslo

More Information

Additional Information:

Information from the Antibiotic Centre for Primary Care 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Eliassen KE, Reiso H, Berild D, Lindbæk 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.

• Responsible Party: Morten Lindbaek, Professor, University of Oslo
• ClinicalTrials.gov Identifier: NCT01368341 History of Changes
• Other Study ID Numbers: EUDRACT 2010-023747
• First Posted: June 7, 2011
• Last Update Posted: December 12, 2014
• Last Verified: December 2014

Keywords provided by Morten Lindbaek, University of Oslo:

Antibiotics; General Practice; Erythema migrans; Borrelia; Ticks

Additional relevant MeSH terms:

Borrelia Infections; Lyme Disease; Erythema Chronicum Migrans; Glossitis, Benign Migratory; Erythema; Skin Diseases; Skin Manifestations; Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Tick-Borne Diseases; Spirochaetales Infections; Skin Diseases, Bacterial; Skin Diseases, Infectious; Infection; Glossitis; Tongue Diseases; Mouth Diseases; Stomatognathic Diseases; Amoxicillin; Doxycycline; Penicillin V; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents