[18F]FDG-PET-CT compared with CT for persistent or recurrent neutropenic fever in high-risk patients (PIPPIN): a multicentre, open-label, phase 3, randomised, controlled trial

Douglas, A; Thursky, K; Spelman, T; Szer, J; Bajel, A; Harrison, S; Tio, SY; Bupha-Intr, O; Tew, M; Worth, L; Teh, B; Chee, L; Ng, A; Carney, D; Khot, A; Haeusler, G; Yong, M; Trubiano, J; Chen, S; Hicks, R; Ritchie, D; Slavin, M

Author(s): Douglas, A; Thursky, K; Spelman, T; Szer, J; Bajel, A; Harrison, S; Tio, SY; Bupha-Intr, O; Tew, M; Worth, L; Teh, B; Chee, L; Ng, A; Carney, D; Khot, A; Haeusler, G; Yong, M; Trubiano, J; Chen, S; Hicks, R; Ritchie, D; Slavin, M;
Details: Publication Year 2022-08,Volume 9,Issue #8,Page e573-e584
Journal Title: Lancet Haematology
Publication Type: Research article
Abstract: BACKGROUND: Management of neutropenic fever in high-risk haematology patients is challenging; there are often few localising clinical features, and diagnostic tests have poor sensitivity and specificity. We aimed to compare how [(18)F]flurodeoxyglucose ([(18)F]FDG)-PET-CT scans and conventional CT scans affected the guidance of antimicrobial management and the outcomes of patients with persistent or recurrent neutropenic fever. METHODS: We did a multicentre, open-label, phase 3, randomised, controlled trial in two tertiary referral hospitals in Australia. We recruited adults aged 18 years or older who were receiving conditioning chemotherapy for haematopoietic stem-cell transplantation or chemotherapy for acute leukaemia and had persistent (>72 h) or recurrent (new fever beyond 72 h of initial onset interspersed with >48 h defervescence) neutropenic fever. Exclusion criteria were pregnancy, allergy to iodinated contrast, or estimated glomerular filtration rate of less than 30 mL/min. Patients were randomly assigned by computer-generated randomisation chart (1:1) to [(18)F]FDG-PET-CT or conventional CT. Masking was not possible because of the nature of the investigation. Scans were done within 3 days of random assignment. The primary endpoint was a composite of starting, stopping, or changing the spectrum (broadening or narrowing) of antimicrobial therapy-referred to here as antimicrobial rationalisation-within 96 h of the assigned scan, analysed per protocol. This trial is registered with clinicaltrials.gov, NCT03429387, and is complete. FINDINGS: Between Jan 8, 2018, and July 23, 2020, we assessed 316 patients for eligibility. 169 patients were excluded and 147 patients were randomly assigned to either [(18)F]FDG-PET-CT (n=73) or CT (n=74). Nine patients did not receive a scan per protocol, and two participants in each group were excluded for repeat entry into the study. 65 patients received [(18)F]FDG-PET-CT (38 [58%] male; 53 [82%] White) and 69 patients received CT (50 [72%] male; 58 [84%] White) per protocol. Median follow up was 6 months (IQR 6-6). Antimicrobial rationalisation occurred in 53 (82%) of 65 patients in the [(18)F]FDG-PET-CT group and 45 (65%) of 69 patients in the CT group (OR 2.36, 95% CI 1.06-5.24; p=0.033). The most frequent component of antimicrobial rationalisation was narrowing spectrum of therapy, in 28 (43%) of 65 patients in the [(18)F]FDG-PET-CT group compared with 17 (25%) of 69 patients in the CT group (OR 2.31, 95% CI 1.11-4.83; p=0.024). INTERPRETATION: [(18)F]FDG-PET-CT was associated with more frequent antimicrobial rationalisation than conventional CT. [(18)F]FDG-PET-CT can support decision making regarding antimicrobial cessation or de-escalation and should be considered in the management of patients with haematological diseases and persistent or recurrent high-risk neutropenic fever after chemotherapy or transplant conditioning. FUNDING: National Health and Medical Research Council Centre of Research Excellence (APP1116876), Melbourne Health foundation, Gilead Research Fellowship grants supported this study.
Keywords: Adult; *Anti-Infective Agents; Female; *Fluorodeoxyglucose F18; Humans; Male; Positron Emission Tomography Computed Tomography/methods; Positron-Emission Tomography; Transplantation Conditioning
Department(s): Infectious Diseases; Health Services Research; Haematology
PubMed ID: 35777413
Publisher's Version: https://doi.org/10.1016/S2352-3026(22)00166-1
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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