Early Discontinuation of Antibiotics in Paediatric High-risk Febrile Neutropenia

Summary

The goal of this clinical trial is to evaluate whether stopping antibiotic treatment early is safe in paediatric patients with cancer who develop high-risk febrile neutropenia but show good clinical evolution and low biomarker levels 48-72 hours after the episode. The main questions it aims to answer are: Is early discontinuation of antibiotics as safe as the standard strategy in terms of preventing invasive bacterial infections (such as sepsis, microbiologically documented infection, ICU admission, or death)? Does this strategy reduce the number of days on antibiotics without increasing infection-related complications? Researchers will compare early antibiotic discontinuation with the standard care strategy to see whether the early-stop approach provides similar safety while reducing antibiotic exposure. Participants will: Receive standard initial antibiotic therapy for febrile neutropenia. Undergo clinical and biomarker evaluations (including CRP and PCT). Be randomly assigned to: Experimental group: early discontinuation of antibiotics, or Control group: continuation of the standard antibiotic strategy. Be followed for 28 days after randomisation to monitor safety outcomes and treatment effects.

Timeline

Start

2026-06-01

Primary completion

2028-07-01

Completion

2028-07-01

Publications

• Background Lucignano B, Cento V, Agosta M, Ambrogi F, Albitar-Nehme S, Mancinelli L, Mattana G, Onori M, Galaverna F, Di Chiara L, Fragasso T, Bianchi R, Tortora F, Auriti C, Dotta A, Cecchetti C, Perdichizzi S, Raponi M, Onetti Muda A, Nerini Molteni S, Villani A, Locatelli F, Perno CF, Bernaschi P. Effective Rapid Diagnosis of Bacterial and Fungal Bloodstream Infections by T2 Magnetic Resonance Technology in the Pediatric Population. J Clin Microbiol. 2022 Oct 19;60(10):e0029222. doi: 10.1128/jcm.00292-22. Epub 2022 Sep 7.
• Background Clancy CJ, Nguyen MH. T2 magnetic resonance for the diagnosis of bloodstream infections: charting a path forward. J Antimicrob Chemother. 2018 Mar 1;73(suppl_4):iv2-iv5. doi: 10.1093/jac/dky050.
• Background Secmeer G, Devrim I, Kara A, Ceyhan M, Cengiz B, Kutluk T, Buyukpamukcu M, Yetgin S, Tuncer M, Uludag AK, Tezer H, Yildirim I. Role of procalcitonin and CRP in differentiating a stable from a deteriorating clinical course in pediatric febrile neutropenia. J Pediatr Hematol Oncol. 2007 Feb;29(2):107-11. doi: 10.1097/MPH.0b013e3180320b5b.
• Background Hemming V, Jakes AD, Shenton G, Phillips B. Prospective cohort study of procalcitonin levels in children with cancer presenting with febrile neutropenia. BMC Pediatr. 2017 Jan 5;17(1):2. doi: 10.1186/s12887-016-0766-8.
• Background Santolaya ME, Alvarez AM, Aviles CL, Becker A, King A, Mosso C, O'Ryan M, Paya E, Salgado C, Silva P, Topelberg S, Tordecilla J, Varas M, Villarroel M, Viviani T, Zubieta M. Predictors of severe sepsis not clinically apparent during the first twenty-four hours of hospitalization in children with cancer, neutropenia, and fever: a prospective, multicenter trial. Pediatr Infect Dis J. 2008 Jun;27(6):538-43. doi: 10.1097/INF.0b013e3181673c3c.
• Background Cost CR, Stegner MM, Leonard D, Leavey P. IL-8 predicts pediatric oncology patients with febrile neutropenia at low risk for bacteremia. J Pediatr Hematol Oncol. 2013 Apr;35(3):206-11. doi: 10.1097/MPH.0b013e318281e653.
• Background Ammann RA, Bodmer N, Hirt A, Niggli FK, Nadal D, Simon A, Ozsahin H, Kontny U, Kuhne T, Popovic MB, Luthy AR, Aebi C. Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study. J Clin Oncol. 2010 Apr 20;28(12):2008-14. doi: 10.1200/JCO.2009.25.8988. Epub 2010 Mar 15.
• Background Ammann RA, Hirt A, Luthy AR, Aebi C. Identification of children presenting with fever in chemotherapy-induced neutropenia at low risk for severe bacterial infection. Med Pediatr Oncol. 2003 Nov;41(5):436-43. doi: 10.1002/mpo.10320.
• Background Santolaya ME, Alvarez AM, Becker A, Cofre J, Enriquez N, O'Ryan M, Paya E, Pilorget J, Salgado C, Tordecilla J, Varas M, Villarroel M, Viviani T, Zubieta M. Prospective, multicenter evaluation of risk factors associated with invasive bacterial infection in children with cancer, neutropenia, and fever. J Clin Oncol. 2001 Jul 15;19(14):3415-21. doi: 10.1200/JCO.2001.19.14.3415.
• Background Rondinelli PI, Ribeiro Kde C, de Camargo B. A proposed score for predicting severe infection complications in children with chemotherapy-induced febrile neutropenia. J Pediatr Hematol Oncol. 2006 Oct;28(10):665-70. doi: 10.1097/01.mph.0000212996.94929.0b.
• Background Alexander SW, Wade KC, Hibberd PL, Parsons SK. Evaluation of risk prediction criteria for episodes of febrile neutropenia in children with cancer. J Pediatr Hematol Oncol. 2002 Jan;24(1):38-42. doi: 10.1097/00043426-200201000-00011.
• Background Rackoff WR, Gonin R, Robinson C, Kreissman SG, Breitfeld PB. Predicting the risk of bacteremia in childen with fever and neutropenia. J Clin Oncol. 1996 Mar;14(3):919-24. doi: 10.1200/JCO.1996.14.3.919.
• Background Santolaya ME, Alvarez AM, Acuna M, Aviles CL, Salgado C, Tordecilla J, Varas M, Venegas M, Villarroel M, Zubieta M, Toso A, Bataszew A, Farfan MJ, de la Maza V, Vergara A, Valenzuela R, Torres JP. Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial. Clin Microbiol Infect. 2017 Mar;23(3):173-178. doi: 10.1016/j.cmi.2016.11.001. Epub 2016 Nov 14.
• Background Aguilar-Guisado M, Espigado I, Martin-Pena A, Gudiol C, Royo-Cebrecos C, Falantes J, Vazquez-Lopez L, Montero MI, Rosso-Fernandez C, de la Luz Martino M, Parody R, Gonzalez-Campos J, Garzon-Lopez S, Calderon-Cabrera C, Barba P, Rodriguez N, Rovira M, Montero-Mateos E, Carratala J, Perez-Simon JA, Cisneros JM. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017 Dec;4(12):e573-e583. doi: 10.1016/S2352-3026(17)30211-9. Epub 2017 Nov 15.
• Background Martinez Campos L, Perez-Albert P, Ferres Ramis L, Rincon-Lopez EM, Mendoza-Palomar N, Soler-Palacin P, Aguilera-Alonso D; en representacion del Grupo de trabajo de Infecciones Bacterianas de la Sociedad Espanola de Infectologia Pediatrica (SEIP); Grupo de Soporte de la Sociedad Espanola de Hematologia y Oncologia Pediatrica (SEHOP); Grupo de trabajo de Infeccion Fungica Invasiva de la Sociedad Espanola de Infectologia Pediatrica (SEIP). Consensus document on the management of febrile neutropenia in paediatric haematology and oncology patients of the Spanish Society of Pediatric Infectious Diseases (SEIP) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP). An Pediatr (Engl Ed). 2023 Jun;98(6):446-459. doi: 10.1016/j.anpede.2023.03.010. Epub 2023 May 31.
• Background Santolaya ME, Contardo V, Torres JP, Lopez-Medina E, Rosanova MT, Alvarez AM, Gutierrez V, Claverie X, Rabello M, Zubieta M, Alvarez-Olmos MI, Camacho G, Perez P, Marino C, Garces C, Coronell W, Lopez P, Gomez S, Epelbaum C. [Management of episodes of febrile neutropenia in children with cancer. Consensus of the Latin American Society of Pediatric Infectious Diseases 2021]. Rev Chilena Infectol. 2021 Dec;38(6):857-909. doi: 10.4067/s0716-10182021000600857. Spanish.
• Background Mattei D, Baretta V, Mazzariol A, Maccacaro L, Balter R, Zaccaron A, Bonetti E, Chinello M, Vitale V, Caddeo G, Esposto MP, Pezzella V, Gibellini D, Tridello G, Cesaro S. Characteristics and Outcomes of Bloodstream Infections in a Tertiary-Care Pediatric Hematology-Oncology Unit: A 10-Year Study. J Clin Med. 2022 Feb 8;11(3):880. doi: 10.3390/jcm11030880.
• Background Lehrnbecher T, Averbuch D, Castagnola E, Cesaro S, Ammann RA, Garcia-Vidal C, Kanerva J, Lanternier F, Mesini A, Mikulska M, Pana D, Ritz N, Slavin M, Styczynski J, Warris A, Groll AH; 8th European Conference on Infections in Leukaemia. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation. Lancet Oncol. 2021 Jun;22(6):e270-e280. doi: 10.1016/S1470-2045(20)30725-7. Epub 2021 Mar 31.
• Background Lehrnbecher T, Robinson PD, Ammann RA, Fisher B, Patel P, Phillips R, Beauchemin MP, Carlesse F, Castagnola E, Davis BL, Elgarten CW, Groll AH, Haeusler GM, Koenig C, Santolaya ME, Tissing WJE, Wolf J, Alexander S, Hu H, Dupuis LL, Sung L. Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update. J Clin Oncol. 2023 Mar 20;41(9):1774-1785. doi: 10.1200/JCO.22.02224. Epub 2023 Jan 23.

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