Tuberculosis Prophylaxis With Levofloxacin in Liver Transplant Patients is Associated With a High Incidence of Tenosynovitis: Safety Analysis of a Multicenter Randomized Trial

Clinical Infectious Diseases. 2015 Jun 1; 60(11): 1642-9

Aims
To evaluate the efficacy and safety of levofloxacin administered to candidates awaiting liver transplantation compared to conventional isoniazid prophylaxis initiated 3-6 months after transplantation.

Interventions
Levofloxacin (500mg) or isoniazid (300mg)

Participants
64 patients randomised to isoniazid (n=31) or levofloxacin (n=33)

Outcomes
Tuberculosis and adverse events.

Follow-up
18 months

CET Conclusions
Prophylaxis for latent TB in liver transplant patients is difficult, as commonly used agents such as isoniazid are hepatotoxic and cannot be commenced until liver function has stabilised post-transplant. This multicentre trial was designed to test the efficacy of levofloxacin, started pre-transplant, as prophylaxis in liver transplant recipients. The control cohort received standard practice of isoniazid prophylaxis commenced post-transplant once the liver function had stabilised. The study aimed to enrol 870 patients, but was discontinued following enrolment of 64 patients due to a high incidence of severe tenosynovitis in the levofloxacin arm. The reason for this are not clear – there was no pharmacokinetic monitoring to determine whether drug exposure was higher than previous studies where incidence of arthralgia and tenosynovitis has been much lower. Any future studies using quinolones as prophylaxis should include careful monitoring of drug levels and recording of adverse events.

Jadad score
3

Data analysis
Strict intention-to-treat analysis

Allocation concealment
No

Trial registration
NCT01761201 and EudraCT 2010-022302-41

Funding source
Non-industry funded