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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Study protocol

Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) - design of a randomized controlled trial of prolonged antibiotic treatment in patients with persistent symptoms attributed to Lyme borreliosis

Authors: Anneleen Berende, Hadewych JM ter Hofstede, A Rogier T Donders, Henriët van Middendorp, Roy PC Kessels, Eddy MM Adang, Fidel J Vos, Andrea WM Evers, Bart Jan Kullberg

Published in: BMC Infectious Diseases | Issue 1/2014

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Abstract

Background

Lyme borreliosis, a potentially severe tick-borne infection caused by Borrelia burgdorferi, can cause multi-system inflammatory disease. The incidence has been increasing, as has the number of patients with persistent symptoms attributed to Borrelia. These symptoms, also referred to as post-Lyme disease syndrome, may follow an erythema migrans or other Lyme manifestations, and include pain, fatigue, and cognitive disturbances. The optimal duration of treatment for these symptoms is a subject of controversy. The PLEASE study is designed to determine whether prolonged antibiotic treatment leads to better patient outcome than standard treatment.

Methods/Design

The PLEASE study is a double-blind, randomized, placebo-controlled trial. Based on power analysis and compensating for possible loss to follow-up, a minimum of 255 patients with borreliosis-attributed persistent symptoms are included. These symptoms are either (a) temporally related to an erythema migrans or otherwise proven symptomatic borreliosis, or (b) accompanied by a positive B. burgdorferi IgG or IgM immunoblot. All patients receive open-label ceftriaxone for two weeks. Patients are then randomized (ratio 1:1:1) to blinded oral follow-up treatment for 12 weeks with (I) doxycycline, (II) clarithromycin combined with hydroxychloroquine, or (III) placebo. The primary outcome is the physical component summary score (PCS) of the RAND-36 Health Status Inventory (RAND SF-36) at week 14. Secondary outcomes include physical and mental aspects of health-related quality of life (assessed by the subscales of the RAND SF-36), fatigue, neuropsychological evaluation, physical activity, and cost-effectiveness.

Discussion

This article describes the background and design issues of the PLEASE study protocol. The results of this study may provide evidence for prescribing or withholding prolonged antibiotic treatment.

Trial registration

ClinicalTrials.gov: NCT01207739, Netherlands Trial Register: NTR2469
Appendix
Available only for authorised users
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Metadata
Title
Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) - design of a randomized controlled trial of prolonged antibiotic treatment in patients with persistent symptoms attributed to Lyme borreliosis
Authors
Anneleen Berende
Hadewych JM ter Hofstede
A Rogier T Donders
Henriët van Middendorp
Roy PC Kessels
Eddy MM Adang
Fidel J Vos
Andrea WM Evers
Bart Jan Kullberg
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-014-0543-y

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