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Prophylactic levofloxacin to prevent infections in newly diagnosed symptomatic myeloma: the TEAMM RCT
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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., Whittaker, Anna C., Hawkey, Peter, Low, Eric and Dunn, Janet A. (2019) Prophylactic levofloxacin to prevent infections in newly diagnosed symptomatic myeloma: the TEAMM RCT. Health Technology Assessment, 23 (62). pp. 1-94. doi:10.3310/hta23620
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Official URL: https://doi.org/10.3310/hta23620
Abstract
Background Myeloma causes profound immunodeficiency and recurrent serious infections. There are approximately 5500 new UK cases of myeloma per annum, and one-quarter of patients will have a serious infection within 3 months of diagnosis. Newly diagnosed patients may benefit from antibiotic prophylaxis to prevent infection. However, the use of prophylaxis has not been established in myeloma and may be associated with health-care-associated infections (HCAIs), such as Clostridium difficile. There is a need to assess the benefits and cost-effectiveness of the use of antibacterial prophylaxis against any risks in a double-blind, placebo-controlled, randomised clinical trial. Objectives To assess the risks, benefits and cost-effectiveness of prophylactic levofloxacin in newly diagnosed symptomatic myeloma patients. Design Multicentre, randomised, double-blind, placebo-controlled trial. A central telephone randomisation service used a minimisation computer algorithm to allocate treatments in a 1 : 1 ratio. Setting A total of 93 NHS hospitals throughout England, Northern Ireland and Wales. Participants A total of 977 patients with newly diagnosed symptomatic myeloma. Intervention Patients were randomised to receive levofloxacin or placebo tablets for 12 weeks at the start of antimyeloma treatment. Treatment allocation was blinded and balanced by centre, estimated glomerular filtration rate and intention to give high-dose chemotherapy with autologous stem cell transplantation. Follow-up was at 4-week intervals up to 16 weeks, with a further follow-up at 1 year. Main outcome measures The primary outcome was to assess the number of febrile episodes (or deaths) in the first 12 weeks from randomisation. Secondary outcomes included number of deaths and infection-related deaths, days in hospital, carriage and invasive infections, response to antimyeloma treatment and its relation to infection, quality of life and overall survival within the first 12 weeks and beyond. Results In total, 977 patients were randomised (levofloxacin, n = 489; placebo, n = 488). A total of 134 (27%) events (febrile episodes, n = 119; deaths, n = 15) occurred in the placebo arm and 95 (19%) events (febrile episodes, n = 91; deaths, n = 4) occurred in the levofloxacin arm; the hazard ratio for time to first event (febrile episode or death) within the first 12 weeks was 0.66 (95% confidence interval 0.51 to 0.86; p = 0.002). Levofloxacin also reduced other infections (144 infections from 116 patients) compared with placebo (179 infections from 133 patients; p-trend of 0.06). There was no difference in new acquisitions of C. difficile, methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase Gram-negative organisms when assessed up to 16 weeks. Levofloxacin produced slightly higher quality-adjusted life-year gains over 16 weeks, but had associated higher costs for health resource use. With a median follow-up of 52 weeks, there was no significant difference in overall survival (p = 0.94). Limitations Short duration of prophylactic antibiotics and cost-effectiveness. Conclusions During the 12 weeks from new diagnosis, the addition of prophylactic levofloxacin to active myeloma treatment significantly reduced febrile episodes and deaths without increasing HCAIs or carriage. Future work should aim to establish the optimal duration of antibiotic prophylaxis and should involve the laboratory investigation of immunity, inflammation and disease activity on stored samples funded by the TEAMM (Tackling Early Morbidity and Mortality in Myeloma) National Institute for Health Research Efficacy and Mechanism Evaluation grant (reference number 14/24/04). Trial registration Current Controlled Trials ISRCTN51731976. Funding details This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 62. See the NIHR Journals Library website for further project information.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QR Microbiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | ||||||
| Library of Congress Subject Headings (LCSH): | Infection -- Prevention, Myeloma proteins, Symptoms, Immunodeficiency | ||||||
| Journal or Publication Title: | Health Technology Assessment | ||||||
| Publisher: | National Institute for Health Research | ||||||
| ISSN: | 2046-4924 | ||||||
| Official Date: | 1 November 2019 | ||||||
| Dates: |
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| Date of first compliant deposit: | 10 February 2020 | ||||||
| Volume: | 23 | ||||||
| Number: | 62 | ||||||
| Page Range: | pp. 1-94 | ||||||
| DOI: | 10.3310/hta23620 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Publisher Statement: | © Queen’s Printer and Controller of HMSO 2019. This work was produced by Drayson et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. | ||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||
| RIOXX Funder/Project Grant: |
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