The Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) is a clinical trial designed to evaluate the efficacy of prolonged antibiotic treatment for patients experiencing persistent symptoms attributed to Lyme borreliosis. This randomized, double-blind, placebo-controlled study addresses the ongoing debate surrounding the optimal duration of antibiotic therapy for individuals who continue to suffer from pain, fatigue, and cognitive disturbances after initial Lyme disease treatment.
Background and Rationale
Lyme borreliosis, caused by the bacterium Borrelia burgdorferi, is a multi-system inflammatory disease transmitted through tick bites. While early Lyme disease is typically treated with a short course of antibiotics, a subset of patients develops persistent symptoms, often referred to as post-Lyme disease syndrome or chronic Lyme disease. These symptoms can significantly impair quality of life, with chronic pain being a major contributor. The incidence of Lyme disease has been increasing, with a parallel rise in patients reporting persistent symptoms, creating a need for evidence-based treatment strategies.
Study Design and Methods
The PLEASE study is a three-arm trial comparing the effects of different antibiotic regimens following initial treatment with ceftriaxone. Patients receive open-label ceftriaxone for two weeks, followed by randomization to one of three groups for 12 weeks:
- Doxycycline
- Clarithromycin combined with hydroxychloroquine
- Placebo
The primary outcome measure is the physical component summary score (PCS) of the RAND-36 Health Status Inventory at week 14. Secondary outcomes include assessments of physical and mental health-related quality of life, fatigue, neuropsychological function, physical activity, and cost-effectiveness.
Patient Population
The study enrolls patients with borreliosis-attributed persistent symptoms, including musculoskeletal pain, arthritis, arthralgia, neuralgia, sensory disturbances, or neuropsychological/cognitive disorders, with or without persistent fatigue. Eligible patients must have symptoms temporally related to an erythema migrans or other proven symptomatic Lyme borreliosis, or have symptoms accompanied by a positive B. burgdorferi IgG or IgM immunoblot. Exclusion criteria include known allergies to tetracyclines, macrolides, hydroxychloroquine, or ceftriaxone, as well as certain co-morbidities and prior antibiotic use.
Significance
The PLEASE study aims to provide clarity on the controversial topic of prolonged antibiotic treatment for persistent Lyme symptoms. By comparing different antibiotic regimens to placebo, the trial seeks to determine whether long-term antibiotic therapy leads to improved patient outcomes. The results of this study could inform clinical guidelines and improve the management of patients with borreliosis-attributed persistent symptoms, addressing a significant unmet medical need.
