Erythema MigransPhase 4NorTick_EMNCT01368341
Comparing 3 Antibiotic Regimes for Erythema Migrans in General Practice
A Phase 4 study testing Doxycycline, Phenoxymethylpenicillin and Amoxicillin in people with Erythema Migrans and Erythema Chronicum Migrans, run by Morten Lindbaek at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Erythema Migrans, Erythema Chronicum Migrans, Borreliosis
- What is being tested?
- Doxycycline, Phenoxymethylpenicillin and Amoxicillin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 225 participants
- Where
- 1 siteNorway
- Study dates
- Jun 2011to Dec 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of Erythema migrans
- Over the age of 18
- Signing an concent form after information in writing
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- Erythema Migrans, Erythema Chronicum Migrans, Borreliosis, Lyme Disease, Early Lyme Disease
- Being tested
- Doxycycline, Phenoxymethylpenicillin, Amoxicillin
- Keywords
- Antibiotics, General Practice, Erythema migrans, Borrelia, Ticks
- Medical subject headings
- Glossitis, Benign Migratory, Erythema Chronicum Migrans, Borrelia Infections, Lyme Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Also called Doksycycline 100 mg HEXAL, no. 30
1 tablet, 100 mg, b.i.d. 14 days
PhenoxymethylpenicillinDrug
Also called Weifapenin 650 mg, WEIFA, no. 100
Tablet 650 mg, 2 tablets, t.i.d., 14 days
AmoxicillinDrug
Also called Amoxicillin 500 mg MYLAN, no. 30 + 20.
Capsula, 500 mg, t.i.d., 14 days
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline | Active comparator | Doxycycline, 100 mg, tablets, b.i.d., 14 days Receives: Drug: Doxycycline |
| Penicillin | Active comparator | Phenoxymethylpenicillin tablets 650 mg. 2 tablets t.i.d. 14 days Receives: Drug: Phenoxymethylpenicillin |
| Amoxicillin | Active comparator | Amoxicillin 500 mg capsula, t.i.d., 14 days Receives: Drug: Amoxicillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1-90 days
Secondary outcomes (5)
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.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 1-14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionDec 2013
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Erythema MigransStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 225 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Morten Lindbaek
- Sponsor type
- University, hospital or other
- Collaborators
- Norwegian Institute of Public Health, Sorlandet Hospital HF, Norwegian University of Life Sciences
- Responsible party
- Sponsor-investigator, Morten Lindbaek, University of Oslo
- Investigators
- Morten Lindbak, Professor, Principal investigator, University of Oslo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01368341
- Sponsor's protocol ID
- EUDRACT 2010-023747
- Acronym
- NorTick_EM
- Status last verified
- Dec 2014
- First submitted
- 6 Jun 2011
- Last updated
- 12 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 29505880
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01368341
- Acronym / sponsor ID
- NorTick_EM / EUDRACT 2010-023747
- Conditions
- Erythema Migrans, Erythema Chronicum Migrans, Borreliosis, Lyme Disease, Early Lyme Disease
- Keywords
- Antibiotics, General Practice, Erythema migrans, Borrelia, Ticks
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 225 participants (estimated)
- Lead sponsor
- Morten LindbaekUniversity, hospital or other
- Collaborators
- Norwegian Institute of Public Health, Sorlandet Hospital HF, Norwegian University of Life Sciences
- Study start
- Jun 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 7 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Doxycycline | Active comparator | Drug: DoxycyclineDoxycycline, 100 mg, tablets, b.i.d., 14 days |
| Penicillin | Active comparator | Drug: PhenoxymethylpenicillinPhenoxymethylpenicillin tablets 650 mg. 2 tablets t.i.d. 14 days |
| Amoxicillin | Active comparator | Drug: AmoxicillinAmoxicillin 500 mg capsula, t.i.d., 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Clinical diagnosis of Erythema migrans
- Over the age of 18
- Signing an concent form after information in writing
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoxycyclineAlso: Doksycycline 100 mg HEXAL, no. 301 tablet, 100 mg, b.i.d. 14 days | Drug | Doxycycline |
| PhenoxymethylpenicillinAlso: Weifapenin 650 mg, WEIFA, no. 100Tablet 650 mg, 2 tablets, t.i.d., 14 days | Drug | Penicillin |
| AmoxicillinAlso: Amoxicillin 500 mg MYLAN, no. 30 + 20.Capsula, 500 mg, t.i.d., 14 days | Drug | Amoxicillin |
Primary outcome
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.
5 secondary outcomes
Subjective Health Complaints (SHC)
Time frame: 1 year
Borrelia antibodies
Time frame: 1-90 days
Side symptoms
Time frame: 1-14 days
Side effects
Time frame: 1-14 days
Subgrouping and TBE
Time frame: 1-14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2014.
- Derived from this study: PubMed 29505880Eliassen 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.
- Information from the Antibiotic Centre for Primary CareLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morten Lindbak, Professor principal investigator
University of Oslo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doxycycline, Phenoxymethylpenicillin and Amoxicillin in people with Erythema Migrans and Erythema Chronicum Migrans, run by Morten Lindbaek at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of Erythema migrans (EM) (time frame: 1-90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01368341, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2014.