Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/30417
Appears in Collections:Faculty of Health Sciences and Sport Journal Articles
Peer Review Status: Refereed
Title: Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial
Author(s): Drayson, Mark T
Bowcock, Stella
Planche, Tim
Iqbal, Gulnaz
Pratt, Guy
Yong, Kwee
Wood, Jill
Raynes, Kerry
Higgins, Helen
Dawkins, Bryony
Meads, David
Hulme, Claire T
Monahan, Irene
Whittaker, Anna C
Karunanithi, Kamaraj
Keywords: myeloma
antibiotic prophylaxis
placebo controlled randomised trial
infection
febrile episodes
deaths
health care associated infections
Issue Date: 23-Oct-2019
Citation: Drayson MT, Bowcock S, Planche T, Iqbal G, Pratt G, Yong K, Wood J, Raynes K, Higgins H, Dawkins B, Meads D, Hulme CT, Monahan I, Whittaker AC & Karunanithi K (2019) Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncology. https://doi.org/10.1016/S1470-2045%2819%2930506-6
Abstract: Background Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. Methods TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. Findings Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8–13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51–0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. Interpretation Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy.
DOI Link: 10.1016/S1470-2045(19)30506-6
Rights: This is an open access article distributed under the terms of the Creative Commons CC-BY license (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You are not required to obtain permission to reuse this article.
Notes: Output Status: Forthcoming/Available Online Additional co-authors: Helen Dignum, Edward Belsham, Jeff Neilson, Beth Harrison, Anand Lokare, Gavin Campbell, Michael Hamblin, Peter Hawkey, Eric Low, Janet A Dunn, for the TEAMM Trial Management Group and Trial Investigators
Licence URL(s): http://creativecommons.org/licenses/by/4.0/

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