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

BMC Infect Dis. 2014 Oct 16;14:543. doi: 10.1186/s12879-014-0543-y.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Bacterial Agents / therapeutic use*
  • Borrelia burgdorferi*
  • Ceftriaxone / therapeutic use
  • Double-Blind Method
  • Doxycycline / administration & dosage
  • Drug Administration Schedule
  • Europe
  • Female
  • Humans
  • Hydroxychloroquine / administration & dosage
  • Lyme Disease / drug therapy*
  • Male
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Hydroxychloroquine
  • Ceftriaxone
  • Doxycycline

Associated data

  • NTR/NTR2469
  • ClinicalTrials.gov/NCT01207739