Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) - a randomized controlled trial of prolonged antibiotic treatment in patients with persistent symptoms attributed to Lyme borreliosis || Abstract #ECCMD-1020
For further information, see LNE topic Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) [March 2011]O150
1-hour Oral Session
Towards a better understanding of Lyme disease
Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) - a randomized controlled trial of prolonged antibiotic treatment in patients with persistent symptoms attributed to Lyme borreliosis
A. Berende, H. ter Hofstede, F. Vos[3,4], R. Donders, H. van Middendorp[6,7], R. Kessels, H. Knoop, M. Vogelaar, M. Tromp, F. van den Hoogen, A. Evers[13,14], B. Kullberg
1. Department of Medicine and Radboud Center for Infectious Diseases- Radboud university medical center, Nijmegen, Netherlands
2. Department of Medicine- Sint Maartenskliniek, Nijmegen, Netherlands
3. Department for Health Evidence- Radboud university medical center, Nijmegen, Netherlands
4. Department of Medical Psychology- Radboud university medical center, Nijmegen, Netherlands
5.Institute of Psychology- Health, Medical, and Neuropsychology Unit, Leiden University, Leiden, Netherlands
6.Department of Medical Psychology and Donders Institute for Brain- Cognition and Behaviour, Radboud university medical center, Nijmegen, Netherlands
7. Expert Centre for Chronic Fatigue- Radboud university medical center, Nijmegen, Netherlands 8Department of Rheumatology- Sint Maartenskliniek, Nijmegen, Netherlands
Major controversy exists about the origin and treatment of persistent symptoms attributed to Borrelia. These symptoms, also referred to as post-Lyme disease syndrome, may follow an erythema migrans or other Lyme manifestations, and may persist despite primary treatment. The present study (PLEASE) is the first randomised, controlled trial in Europe to determine whether prolonged antibiotic treatment leads to better outcomes than standard treatment in patients with borreliosis-attributed persistent symptoms.
In this nationwide, double-blind, randomised, placebo-controlled study, patients were included with borreliosis-attributed persistent symptoms (e.g., pain and sensory or cognitive disturbances), either temporally related to a proven symptomatic borreliosis or accompanied by a positive B. burgdorferi IgG or IgM immunoblot. All patients received open-label ceftriaxone for 2 weeks and were then randomised (ratio 1:1:1) to blinded oral follow-up treatment for 12 weeks with doxycycline, clarithromycin combined with hydroxychloroquine, or placebo. Randomisation was computerised and balanced by minimisation for age, gender, duration of symptoms, and baseline Global Health Composite score of the RAND-36 Health Status Inventory (RAND SF-36). The primary outcome was the health-related quality of life at End of Treatment (EOT, week 14), assessed by the physical component summary score (PCS) of the RAND SF-36. Analysis of covariance, correcting for baseline PCS and gender, was used to compare the three treatment arms. Follow-up was performed at 26, 40, and 52 weeks. Secondary outcomes included physical and mental aspects of health-related quality of life (RAND SF-36 subscales), fatigue, cognitive performance, and physical activity.
Of 281 patients randomised, 280 were included in the modified intention-to-treat analysis: 86 patients randomised to doxycycline, 96 to clarithromycin/hydroxychloroquine, and 98 to placebo. Baseline characteristics were similar in all treatment groups. The mean PCS was significantly improved at EOT compared to baseline (p<0.001, for all groups). At EOT, the PCS did not differ significantly between the three treatment arms (p>.05), and remained similar across the groups during follow-up until week 52 (p>.05). None of the secondary outcomes studied yielded significant differences between the groups. Adverse events were similar between groups (p>.05). Four drug-related serious adverse events occurred during treatment with ceftriaxone, and one during clarithromycin/hydroxychloroquine.
Long-term treatment with 2 weeks of ceftriaxone followed by 12 weeks of doxycycline or clarithromycin/hydroxychloroquine does not significantly improve quality of life compared to short-term treatment in patients with persistent symptoms attributed to Lyme borreliosis. (Funded by the Netherlands Organization for Health Research and Development; ClinicalTrials.gov: NCT01207739).