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Persistent Lyme Empiric Antibiotic Study Europe (PLEASE)

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ClinicalTrials.gov Identifier: NCT01207739
Recruitment Status : Completed
First Posted : September 23, 2010
Last Update Posted : September 8, 2016
Sponsor:
Collaborators:
Sint Maartenskliniek
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Radboud University

Tracking Information
First Submitted Date  ICMJE September 22, 2010
First Posted Date  ICMJE September 23, 2010
Last Update Posted Date September 8, 2016
Study Start Date  ICMJE September 2010
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2014)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
Global score 36-item Short-form General Health Survey (SF 36) [ Time Frame: Week 14 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2014)
  • 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).
  • Actometer recording during 14 days (objective physical activity) [ Time Frame: weeks 0, 14 and 40 ]
  • Measurements of neuropsychological impairment [ Time Frame: weeks 0, 14, 26 and 40 ]
  • 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).
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
  • Subscales 36-item Short-form General Health Survey (SF 36) [ Time Frame: weeks 0, 14, 26 and 40 ]
  • Actometer recording during 14 days (objective physical activity) [ Time Frame: weeks 0, 14 and 40 ]
  • Measurements of neuropsychological impairment [ Time Frame: weeks 0, 14, 26 and 40 ]
  • Economic evaluation: Questionaire EQ-5D, health consumption and productivity of labour [ Time Frame: weeks 0, 14, 26 and 40 ]
  • Fatigue subscale of Checklist Individual Strength (CIS) [ Time Frame: weeks 0, 14, 26, and 40 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Persistent Lyme Empiric Antibiotic Study Europe
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Lyme Disease
  • Borrelia Infection
Intervention  ICMJE
  • Drug: Doxycycline
    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)
  • Drug: Clarithromycin and hydroxychloroquine
    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)
  • Drug: Placebo
    After open-label i.v. ceftriaxone 2000 mg qd via a peripheral i.v. catheter: 12 weeks' course of double placebo b.i.d.
Study Arms  ICMJE
  • Active Comparator: Doxycycline
    Intervention: Drug: Doxycycline
  • Active Comparator: Clarithromycin and hydroxychloroquine
    Intervention: Drug: Clarithromycin and hydroxychloroquine
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2014)
280
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2010)
270
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01207739
Other Study ID Numbers  ICMJE PLEASE
NL-27344.091.09 ( Other Grant/Funding Number: ZonMW )
2009-010939-40 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Radboud University
Study Sponsor  ICMJE Radboud University
Collaborators  ICMJE
  • Sint Maartenskliniek
  • ZonMw: The Netherlands Organisation for Health Research and Development
Investigators  ICMJE
Principal Investigator: Bart-Jan Kullberg, Prof., M.D. Radboud University
PRS Account Radboud University
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP