Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial

Summary Background Use of intravenous penicillin and ceftriaxone to treat Lyme neuroborreliosis is well documented, although oral doxycycline could be a cost-effective alternative. We aimed to compare the efficacy of oral doxycycline with intravenous ceftriaxone for the treatment of Lyme neuroborreliosis. Methods From April, 2004, to October, 2007, we recruited consecutive adult patients from nine hospitals in southern Norway into a non-inferiority trial. Inclusion criteria were neurological symptoms suggestive of Lyme neuroborreliosis without other obvious causes, and presence of any of the following: a CSF white-cell count of more than five per mL; intrathecal production of specific Borrelia burgdorferi antibodies; or acrodermatitis chronicum atrophicans. Patients were randomly allocated to receive 200 mg oral doxycycline or 2 g intravenous ceftriaxone once per day for 14 days, in a double-blind, double-dummy design. A composite clinical score (range 0 to 64, 0=best) was based on standardised interviews and clinical neurological examination. The primary outcome was reduction in clinical score at 4 months after the start of treatment. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT00138801. Findings Of 118 patients who underwent randomisation, 102 completed the study (mean clinical score at baseline 8•5 [SD 4•1]). 4 months after the start of treatment, mean score improvement in the doxycycline group (n=54) was 4•5 (95% CI 3•6 to 5•5) points and that in the ceftriaxone group (n=48) was 4•4 (3•4 to 5•4) points (95% CI for difference between groups −0•9 to 1•1; p=0•84). 26 (48%) patients in the doxycycline group and 16 (33%) in the ceftriaxone group had total recovery (95% CI for difference between groups −4% to 34%; p=0•13). Side-effects possibly related to treatment were reported in 21 (37%) and 26 (46%) patients in these groups, respectively (−28% to 9%; p=0•30). Three patients discontinued ceftriaxone treatment owing to adverse events. Interpretation Oral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis. Funding Sørlandet Kompetansefond.