Oral Doxycycline Compared to Intravenous Ceftriaxone in the Treatment of Lyme Neuroborreliosis: A Multicenter, Equivalence, Randomized, Open-label Trial.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
26 04 2021
Historique:
received: 07 01 2020
accepted: 01 03 2020
pubmed: 7 3 2020
medline: 21 5 2021
entrez: 6 3 2020
Statut: ppublish

Résumé

Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally. Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. NCT01635530 and EudraCT 2012-000313-37.

Sections du résumé

BACKGROUND
Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB.
METHODS
Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months.
RESULTS
Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally.
CONCLUSIONS
Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB.
CLINICAL TRIALS REGISTRATION
NCT01635530 and EudraCT 2012-000313-37.

Identifiants

pubmed: 32133487
pii: 5781128
doi: 10.1093/cid/ciaa217
doi:

Substances chimiques

Anti-Bacterial Agents 0
Ceftriaxone 75J73V1629
Doxycycline N12000U13O

Banques de données

ClinicalTrials.gov
['NCT01635530']
EudraCT
['EudraCT 2012-000313-37']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1323-1331

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Auteurs

Elisa Kortela (E)

Department of Clinical Medicine, University of Turku, Turku, Finland.
Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Mari J Kanerva (MJ)

Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Juha Puustinen (J)

Unit of Neurology, Satakunta Central Hospital, Pori, Finland.
Department of Neurology, University of Turku, Turku, Finland.
Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland.

Saija Hurme (S)

Department of Biostatistics, University of Turku, Turku, Finland.

Laura Airas (L)

Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.

Anneli Lauhio (A)

Finnish Medicines Agency, Helsinki, Finland.

Ulla Hohenthal (U)

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

Päivi Jalava-Karvinen (P)

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

Tuomas Nieminen (T)

Infectious Diseases Unit, Satakunta Central Hospital, Pori, Finland.

Taru Finnilä (T)

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

Tony Häggblom (T)

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

Annukka Pietikäinen (A)

Institute of Biomedicine, University of Turku, Turku, Finland.

Mari Koivisto (M)

Department of Biostatistics, University of Turku, Turku, Finland.

Johanna Vilhonen (J)

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

Minna Marttila-Vaara (M)

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

Jukka Hytönen (J)

Institute of Biomedicine, University of Turku, Turku, Finland.
Clinical Microbiology, Turku University Hospital, Turku, Finland.

Jarmo Oksi (J)

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

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