The results of this study may provide evidence for prescribing or withholding prolonged antibiotic treatment. Trial registration ClinicalTrials.gov: “type”:”clinical-trial”,”attrs”:”text”:”NCT01207739″,”term_id”:”NCT01207739″NCT01207739, Netherlands Trial Register: NTR2469 Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0543-y) contains supplementary material, which is available to authorized users. seems to increase as well. to authorized users. seems to increase as well. These borreliosis-attributed persistent symptoms, also referred to as post-Lyme disease syndrome, chronic Lyme disease, or (true or presumed) persistent Lyme disease, may follow an EM or other, possibly unnoticed, manifestations of early Lyme disease, regardless of initial appropriate antibiotic treatment. Patients mainly present with pain, fatigue, neurological, and cognitive disturbances [6]-[8]. Three months after treatment of an EM, the prevalence of these symptoms can be as high as 25% [9]. Although this percentage tends to decrease as more time GR148672X elapses, symptoms are often disabling, and influence the daily life of these patients. Especially chronic pain has been shown to be an important contributor to impairment of health-related quality of life, and is similar to that reported by patients with osteoarthritis [10]. So far, no general, well-accepted definition of the syndrome of borreliosis-associated persistent symptoms exists [11]. This has resulted in a lack of data GR148672X on its incidence and prevalence, and has contributed to misunderstandings and controversy. This controversy especially relates to the pathogenesis of borreliosis-attributed prolonged symptoms: whether they emerge from an ongoing illness, are a post-infectious problem, or are not related to a illness at all. Currently available diagnostic tools (primarily based on serology) are appropriate for the analysis of early Lyme disease in most cases, but have little value for the analysis of potentially prolonged illness [12]. As IgG antibodies against may persist for many months and even years after acute illness, positive serology is not an indication of active or prolonged illness [13],[14]. As long as there is no specific laboratory test for active illness, the decision whether and how long individuals with prolonged symptoms should be treated depends on evidence from medical studies. However, as this evidence has not been consistent, two different methods exist for individuals with borreliosis-attributed prolonged symptoms: (1) standard short-term treatment for 2-4 weeks, as recommended for most manifestations of Lyme borreliosis from the Infectious Diseases Society of America (IDSA) [15] or NMYC (2) long-term treatment for at least 3 months, as recommended from the International Lyme and Associated Diseases Society (ILADS) [16]. Earlier randomized medical tests have not convincingly shown beneficial effects of long term antibiotic treatment [10],[17],[18], and have been subject of ongoing argument [19]. To obtain more insight into the ideal treatment regimen for individuals with borreliosis-attributed prolonged symptoms, we designed a double-blind, randomized medical trial to compare short- versus long-term treatment. With this 3-arm study, entitled Prolonged Lyme Empiric Antibiotic Study Europe (PLEASE), ceftriaxone followed by doxycycline (arm 1) or ceftriaxone followed by the combination of clarithromycin and hydroxychloroquine (arm 2) are compared to short-term therapy with ceftriaxone followed by placebo (arm 3). Here, we describe the study protocol. Methods/Design Study design A randomized, double-blind, placebo-controlled trial is performed to determine whether long-term antibiotic treatment (ceftriaxone followed by doxycycline or ceftriaxone followed by the combination of clarithromycin and hydroxychloroquine) prospects to better patient end result than short-term treatment (ceftriaxone followed by placebo) in individuals with borreliosis-attributed prolonged symptoms. This prospective 3-arm study is carried out at two sites in the Netherlands, the Radboud university or college medical center (Radboudumc) and the Sint Maartenskliniek, and has been authorized by the Medical Ethics Review Committee CMO Regio Arnhem-Nijmegen (sign up quantity 2009/187, NL27344.091.09). The study is conducted in accordance with the principles stated in the most recent version of the Declaration of Helsinki and the International Conference on Harmonisation (ICH) recommendations on Good Clinical Practice. Study populace All individuals are recruited from your outpatient clinic of the Radboudumc, after nationwide referral by physicians. The Radboudumc serves as one of the tertiary referral centers for the Netherlands’ populace of around 17 million. Screening is done using standard medical and laboratory protocols. Eligibility is assessed by a physician relating to specific inclusion and exclusion criteria (Table ?(Table1).1). In short, individuals with borreliosis-attributed prolonged symptoms (musculoskeletal pain, arthritis, arthralgia, neuralgia, sensory disturbances, or neuropsychological/cognitive disorders, with or without prolonged fatigue) are eligible if these symptoms are either GR148672X (a) temporally related to an erythema migrans or otherwise verified symptomatic borreliosis, or (b) accompanied by a positive IgG or IgM immunoblot. An qualified patient is definitely asked to sign educated consent after obtaining written information about the study. Table 1 Inclusion and exclusion criteria antibodies)Bor accompanied by a positive IgG or IgM immunoblot (as defined by strict criteria good European Union Concerted Action on Lyme Borreliosis (EUCALB) and the manufacturer of the immunoblot* [20],[21]), no matter prior ELISA IgG/IgM screening results3Subjects must sign a written.
