Persistent Lyme Empiric Antibiotic Study Europe - Full Text View

Purpose

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.

Condition	Intervention	Phase
Lyme Disease Borrelia Infection	Drug: Doxycycline Drug: Clarithromycin and hydroxychloroquine Drug: Placebo	Phase 4


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

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Lyme Disease

Drug Information available for: Hydroxychloroquine Doxycycline Hydroxychloroquine sulfate Doxycycline monohydrate Doxycycline hyclate Ceftriaxone Clarithromycin Doxycycline calcium

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:

Global score 36-item Short-form General Health Survey (SF 36) [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
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 Outcome Measures:

Subscales 36-item Short-form General Health Survey (SF 36) [ Time Frame: weeks 0, 14, 26, 40 and 52 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Measurements of neuropsychological impairment [ Time Frame: weeks 0, 14, 26 and 40 ] [ Designated as safety issue: No ]
Economic evaluation: Questionaire EQ-5D, health consumption and productivity of labour [ Time Frame: weeks 0, 14, 26, 40 and 52 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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).


Enrollment:	280
Study Start Date:	September 2010
Study Completion Date:	October 2014
Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Doxycycline	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)
Active Comparator: Clarithromycin and hydroxychloroquine	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)
Placebo Comparator: Placebo	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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01207739

Locations


Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sint Maartenskliniek
Nijmegen, Netherlands, 6522 JV

Sponsors and Collaborators

Radboud University

Sint Maartenskliniek

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators


Principal Investigator:	Bart-Jan Kullberg, Prof., M.D.	Radboud University

More Information

Publications:

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. doi: 10.1056/NEJMoa1505425.

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.


Responsible Party:	Radboud University
ClinicalTrials.gov Identifier:	NCT01207739 History of Changes
Other Study ID Numbers:	PLEASE NL-27344.091.09 2009-010939-40
Study First Received:	September 22, 2010
Last Updated:	September 6, 2016
Health Authority:	Netherlands: Medical Ethics Review Committee (METC) Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:


Prolonged antibiotic treatment in Lyme disease Doxycycline Clarithromycin Hydroxychloroquine

Additional relevant MeSH terms:


Lyme Disease Borrelia Infections Gram-Negative Bacterial Infections Bacterial Infections Tick-Borne Diseases Spirochaetales Infections Anti-Bacterial Agents Doxycycline Clarithromycin Ceftriaxone Antibiotics, Antitubercular Hydroxychloroquine	Anti-Infective Agents Antitubercular Agents Antimalarials Antiprotozoal Agents Antiparasitic Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antirheumatic Agents

ClinicalTrials.gov processed this record on September 29, 2016