Persistent Lyme Empiric Antibiotic Study Europe

Lyme Disease Clinical Trial

— PLEASE  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01207739
• Other study ID #: PLEASE
• Secondary ID: NL-27344.091.092
• Status: Completed
• Phase: Phase 4
• First received: September 22, 2010
• Last updated: September 6, 2016
• Start date: September 2010
• Est. completion date: October 2014

Study information

• Verified date: September 2016
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: October 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Borrelia Infection
• Lyme Disease

Intervention

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
• 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
• 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.

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen
Netherlands	Sint Maartenskliniek	Nijmegen

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University	Sint Maartenskliniek, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

Berende A, ter Hofstede HJ, Donders AR, van Middendorp H, Kessels RP, Adang EM, Vos FJ, Evers AW, Kullberg BJ. 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. — View Citation

Berende A, ter Hofstede HJ, Vos FJ, van Middendorp H, Vogelaar ML, Tromp M, van den Hoogen FH, Donders AR, Evers AW, Kullberg BJ. Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. N Engl J Med. 2016 Mar 31;374(13):1209-20. d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global score 36-item Short-form General Health Survey (SF 36)	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.	Week 14	No
Secondary	Subscales 36-item Short-form General Health Survey (SF 36)	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).	weeks 0, 14, 26, 40 and 52	No
Secondary	Actometer recording during 14 days (objective physical activity)		weeks 0, 14 and 40	No
Secondary	Measurements of neuropsychological impairment		weeks 0, 14, 26 and 40	No
Secondary	Economic evaluation: Questionaire EQ-5D, health consumption and productivity of labour	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).	weeks 0, 14, 26, 40 and 52	No
Secondary	Fatigue subscale of Checklist Individual Strength (CIS)	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).	weeks 0, 14, 26, 40 and 52	No