PLEASE Persistent Lyme Empiric Antibiotic Study Europe. A prospective, randomised study comparing two prolonged oral antibiotic strategies after initial intravenous ceftriaxone therapy for patients with symptoms of proven or possible persistent Lyme disease - PLEASE

Phase 1

• Conditions: Persistent Lyme diseasePersistent borreliosis; MedDRA version: 12.0Level: LLTClassification code 10025169Term: Lyme disease; MedDRA version: 12.0Level: LLTClassification code 10025170Term: Lyme's disease; MedDRA version: 12.0Level: LLTClassification code 10067559Term: Lyme borreliosis; MedDRA version: 12.0Level: LLTClassification code 10006036Term: Borrelia burgdorferi infection; MedDRA version: 12.0Level: LLTClassification code 10061591Term: Borrelia infection

• Registration Number: EUCTR2009-010939-40-NL
• Lead Sponsor: MCN St Radboud

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-07-20
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

a.Males or non-pregnant, non-lactating females who are 18 years or older.
b.Women of child-bearing potential must agree to use contraception methods other than oral contraceptives during the study therapy period, since failure of oral contraceptives due to long-term antibiotic use has been described and doxycycline might be teratogenic.
c.Patients with presumed or proven PLD. In this study, clinical suspicion of PLD is defined as complaints of musculoskeletal pain, arthritis or arthralgia, neuralgia, neuropsychological or cognitive disorders, and persistent fatigue, that are:
(a) temporally related to an episode of erythema migrans or otherwise proven symptomatic Lyme disease (defined as within 4 months after erythema migrans as assessed by a physician, or positive biopsy, PCR, culture, intrathecal B. burgdorferi antibodies), OR
(b) accompanied by a positive B. burgdorferi IgG or IgM immunoblot (as defined by strict criteria in line with the European Union Concerted Action on Lyme Borreliosis (EUCALB); regardless of prior ELISA IgG/IgM screening results.
d.Subjects must sign a written informed consent form.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

a.Subjects with a known history of allergy or intolerance to tetracyclines, macrolides, hydroxychloroquine or ceftriaxone.
b.Subjects who have had more than 5 days of antimicrobial therapy with activity against B. burgdorferi within the previous 4 weeks.
c.Subjects with a presumed diagnosis of neuroborreliosis (CSF pleiocytosis or intrathecal antibody production) for which intravenous antimicrobial therapy is required.
d.Subjects with a known diagnosis of HIV-seropositivity or other immune disorders. (No HIV serologic testing is required for the study).
e.Subjects with positive syphilis serology or signs of other spirochetal diseases.
f.Subjects with moderate or severe liver disease defined as alkaline phosphatase, ALAT, or ASAT greater than 3 times upper limit of normal.
g.Subjects who are receiving and cannot discontinue cisapride, astemizole, terfenadine, barbiturates, phenytoin, or carbamazepine (The concentrations of these drugs may increase during claritromycin therapy and/or lead to reduced availability of doxycycline).
h.Subjects who are currently enrolled on other investigational drug trials or receiving investigational agents.
i.Subjects who have been previously randomized into this study.
j. Severe physical or psychiatric co-morbidity that interferes with participation in the study protocol, including previous medical diagnosis of rheumatic conditions, chronic fatigue syndrome or chronic pain conditions as well as insufficient command of the Dutch language.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary goal of the study is to establish whether prolonged antibiotic treatment of patients diagnosed with presumed persistent Lyme disease (as endorsed by the international ILADS guidelines) is efficient and leads to better patient outcome than short-term treatment as endorsed by the Dutch CBO guidelines.;Secondary Objective: Secondary objectives will be studied in an explorative way. The secondary goals include the effect of randomised treatment modalities on physical functioning, psychological functioning, social behaviour, cognitive functioning, and safety. Moreover, cost-effectiveness will be determined by assessment of costs from societal perspective and quality-adjusted life years;Primary end point(s): The primary endpoint is defined as mean functional impairment and pain scores, as measured by the physical functioning scale of the 36-item Short-form General Health Survey (SF 36) and the McGill Pain Questionnaire (MPQ) at EOT (week 14).