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Completed

NCT Number: NCT01207739

Persistent Lyme Empiric Antibiotic Study Europe

The purpose of the study is to establish whether prolonged antibiotic treatment of patients diagnosed with proven or presumed PLD (as endorsed by the international ILADS guidelines) leads to better patient outcome than short-term treatment as endorsed by the Dutch CBO guidelines.

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Key information

Conditions

Lyme Disease Bacterial Infections Bacterial Infections and Mycoses Borrelia Infection Borrelia Infections Gram-Negative Bacterial Infections Infections Spirochaetales Infections Tick-Borne Diseases Vector Borne Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Males or non-pregnant, non-lactating females who are 18 years or older.
  • 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.
  • Patients with presumed or proven PLD. In this study, clinical suspicion of PLD is defined as complaints of musculoskeletal pain, arthritis or arthralgia, neuralgia or sensory disturbances (such as paresthesias or dysesthesias), neuropsychological or cognitive disorders, and persistent fatigue, that are:
  • 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
  • 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.
  • Subjects must sign a written informed consent form.

Exclusion criteria

  • Subjects with a known history of allergy or intolerance to tetracyclines, macrolides, hydroxychloroquine or ceftriaxone.
  • Subjects who have had more than 5 days of antimicrobial therapy with activity against B. burgdorferi within the previous 4 weeks.
  • Subjects with a presumed diagnosis of neuroborreliosis (CSF pleocytosis or intrathecal antibody production) for which intravenous antimicrobial therapy is required.
  • Subjects with a known diagnosis of HIV-seropositivity or other immune disorders. (No HIV serologic testing is required for the study).
  • Subjects with positive syphilis serology or signs of other spirochetal diseases.
  • Subjects with moderate or severe liver disease defined as alkaline phosphatase, ALAT, or ASAT greater than 3 times upper limit of normal.
  • Subjects who are receiving and cannot discontinue cisapride, astemizole, terfenadine, barbiturates, phenytoin, or carbamazepine (The concentrations of these drugs may increase during clarithromycin therapy and/or lead to reduced availability of doxycycline).
  • Subjects who are currently enrolled on other investigational drug trials or receiving investigational agents.
  • Subjects who have been previously randomized into this study.
  • 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.
  • Co-morbidity that could (partially) account for the symptoms of the subject (e.g. vitamin B12 deficiency, anemia, hypothyroidism).

Treatment and study plan

Doxycycline

Drug

After open-label i.v. ceftriaxone 2000 mg qd via a peripheral i.v. catheter: oral Doxycycline 100 mg combined with a placebo b.i.d. for 12 weeks

Other names: Doxycycline disper, CASnr 564-25-0 (doxycycline); 17086-28-1 (doxycycline monohydraat)

Clarithromycin and hydroxychloroquine

Drug

After open-label i.v. ceftriaxone 2000 mg qd via a peripheral i.v. catheter: clarithromycin 500 mg combined with hydroxychloroquine 200 mg b.i.d. for 12 weeks

Other names: Clarithromycine Mylan, RVG 32619, CASnr 81103-11-9, Hydroxychloroquine; Plaquenil, RVG 00853, CASnr 118-42-3 (hydroxychloroquine); 737-36-4 (hydroxychloroquine sulfate)

Placebo

Drug

After open-label i.v. ceftriaxone 2000 mg qd via a peripheral i.v. catheter: 12 weeks' course of double placebo b.i.d.

Primary outcomes

  1. Global score 36-item Short-form General Health Survey (SF 36)

    Time frame: Week 14

    Because different operationalizations of the term 'Global score 36-item Short-form General Health Survey (SF 36)' exist, the primary outcome measure is specified here as the 'physical component summary score' (PCS) of the RAND-36 Health Status Inventory (RAND SF-36, Hays 1998), which is similar to the Medical Outcomes Study (MOS) 36-item Short-Form General Health Survey (SF-36). The PCS is also known as the physical health composite score (PHC). This specification has been communicated to the local Ethics Committee on March 1, 2011, and was approved on April 6, 2011.

Secondary outcomes

  1. Subscales 36-item Short-form General Health Survey (SF 36)

    Time frame: weeks 0, 14, 26, 40 and 52

    After the last comprehensive outcome assessment at week 40, patients are surveyed by post-study questionnaires at week 52 (protocol version 3.8; dated July 17, 2009; final Ethics Committee approval April 29, 2010).

  2. Actometer recording during 14 days (objective physical activity)

    Time frame: weeks 0, 14 and 40

  3. Measurements of neuropsychological impairment

    Time frame: weeks 0, 14, 26 and 40

  4. Economic evaluation: Questionaire EQ-5D, health consumption and productivity of labour

    Time frame: weeks 0, 14, 26, 40 and 52

    After the last comprehensive outcome assessment at week 40, patients are surveyed by post-study questionnaires at week 52 (protocol version 3.8; dated July 17, 2009; final Ethics Committee approval April 29, 2010).

  5. Fatigue subscale of Checklist Individual Strength (CIS)

    Time frame: weeks 0, 14, 26, 40 and 52

    After the last comprehensive outcome assessment at week 40, patients are surveyed by post-study questionnaires at week 52 (protocol version 3.8; dated July 17, 2009; final Ethics Committee approval April 29, 2010).

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

  • Sint Maartenskliniek
  • ZonMw: The Netherlands Organisation for Health Research and Development

Registry information

Official study title

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

Acronym: PLEASE

Important dates

Study start
2010
Primary completion
2013
Study completion
2014
First posted
Sep 23, 2010
Registry last updated
Sep 8, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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