Antibiotic Stewardship in Suspected Neutropenic Fever (ASTERIC Trial)

NCT06794320 | Not Yet Recruiting DMC

• 2 other identifiers: ASTERIC21222361
• Study Type: interventional
• Target: 648
• Locations: 1 country
• Sites: 1

Brief Summary

Executive Summary Background: Neutropenic Fever (NF), or febrile neutropenia, occurs in patients with early stage and metastatic solid tumours, non-leukaemic haematological cancers and acute leukaemia. It has a crude mortality rate of 3 to 18%. In Hong Kong, and in line with international guidelines, the target time from ED registration to ultra-broad spectrum antibiotic (UBSA) administration (door-to-antibiotic time, DTA time) is one hour disregarding the absolute neutrophil count (ANC). However, over 80% patients presenting to hospital with suspected NF (sNF) do not have NF and do not require UBSAs. Thus there is a need for evidence for a safe role for early treatments in patients with sNF to reduce unnecessary use of antibiotics. Protocol, Eligibility and Randomisation: This protocol describes the ASTERIC Trial, a pragmatic, multi-centre, type 1, hybrid effectiveness-implementation, stepped-wedge, before and after, cluster randomised controlled trial with variable baseline and follow up periods. Hospitals will be randomised to start dates comparing usual standard of care (SoC) (Period 1, before) with a new antibiotic stewardship protocol (Period 2, after). Hospitals, not patients, are randomised to variable start dates. The evidence for starting early UBSAs in patients with NF is well-established. What is unclear is how to optimise personalised care and the start times of UBSA when the majority of sNF patients do not have NF, there are delays to receiving an ANC report, and a proportion of patients might not need hospital admission. Study design: a multi-centre, hybrid type 1 effectiveness-implementation trial which is an appropriate study design to evaluate the real-world effectiveness of an antibiotic stewardship protocol; and the barriers to and facilitators of its implementation in the ED setting. Settings: Eight hospitals in Hong Kong with patient involvement 24/7. Outcomes: The Trial has two co-primary outcomes 1) mean total dose of UBSAs prescribed in 7 days and censored at 30 days from the time of randomisation; 2) safety (defined as the proportion of patients with a SAE), censored at 30 days from the time of randomisation. This multifaceted trial addresses three broad domains of implementation according to Proctor's conceptual framework and taxonomy which incorporates the RE-AIM framework, namely: Service Outcomes; Implementation Outcomes and Client outcomes. Simplicity on the frontline: Patient enrolment and other front-line trial procedures will be streamlined. Informed consent is brief and simple and required for follow-up. Follow-up information may be ascertained by contacting participants in person, by phone or electronically, or by review of medical records and databases. Data to be collected: Information will be collected on the patient, age, sex, major co-morbidity, sNF symptom onset date and severity, as well as any contraindications to study treatments. Follow-up information includes antibiotics - name, dose and duration; SAEs; mortality; sepsis; length of hospital stay; cost-effectiveness; patient satisfaction. Numbers: 648 patients (324 patients in each group) adult patients with sNF ≥38.3ºC and Modified Early Warning Score ≤6 within 24 hours of ED registration. Benefit to Healthcare/Expected results: Study results will inform health policy with improvement in hospital services in treating stable sNF evidenced by improved personalised, safe antibiotic stewardship, early antibiotic de-escalation, early discharge, and reduced costs and length of stay. The ASTERIC protocol safely reduces the type, duration and dose of antibiotics.

Conditions

Neutropenic Fever

Keywords

Antibiotic stewardship; Cancer; Carcinoma; Emergency care; Emergency department; Febrile Neutropenia; Health policy; Hematologic Neoplasms; Hospitalization; Length of stay; Meropenem; Neoplasms; Neutrophils; Oncology; Randomized Controlled Trial; RCT; Safety; Tumor

Outcome Measures

Primary Outcomes (2)

• 7-day mean UBSA dose

  Outcome 1 measure: The mean total UBSA dose per patient from ED registration \[Continuous\]

  Up to 7-days

• 30-day Severe Adverse Events

  Outcome 2 measure: The proportion of patients with an SAE \[Binary Y/N\]

  Up to 30-days

Secondary Outcomes (2)

• Mortality

  Up to 30-days

• Length of Hospital Stay

  Up to 30-days

Other Outcomes (19)

• Secondary Service Outcomes: Efficiency

  30-days

• Safety

  30-days

• Effectiveness in UBSA use

  7-days

Study Arms (2)

Period 1(Before): Standard of Care(SoC) + Neutropenic Fever(NF) Protocol

OTHER

Other: NF Protocol

Period 2(After): SoC + ASTERIC Protocol

OTHER

The ASTERIC protocol seeks to evaluate and address barriers and facilitators to a fast-track ANC service coupled with prudent, timely antibiotic stewardship and assessment of admission.

Other: ASTERIC protocol

Interventions

NF Protocol OTHER

The daily practice of physicians in evaluating and treating patients with sNF.

Period 1(Before): Standard of Care(SoC) + Neutropenic Fever(NF) Protocol

ASTERIC Protocol OTHER

i. Risk-assessment tools

Period 2(After): SoC + ASTERIC Protocol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years
• Tympanic temperature ≥38.3ºC within 24 hours before ED registration
• Last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leukaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma, or recipient of HSCT.

You may not qualify if:

• \- The decision on how far to apply or deviate from a protocol rests with the clinician. Patients would be excluded from follow up if were unable or unwilling to provide informed consent for data access

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong

Location

Related Publications (15)

• Peyrony O, Gerlier C, Barla I, Ellouze S, Legay L, Azoulay E, Chevret S, Fontaine JP. Antibiotic prescribing and outcomes in cancer patients with febrile neutropenia in the emergency department. PLoS One. 2020 Feb 28;15(2):e0229828. doi: 10.1371/journal.pone.0229828. eCollection 2020.

  PMID: 32109264 BACKGROUND

• Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073.

  PMID: 21258094 BACKGROUND

• Zhu J, Zhou K, Jiang Y, Liu H, Bai H, Jiang J, Gao Y, Cai Q, Tong Y, Song X, Wang C, Wan L. Bacterial Pathogens Differed Between Neutropenic and Non-neutropenic Patients in the Same Hematological Ward: An 8-Year Survey. Clin Infect Dis. 2018 Nov 13;67(suppl_2):S174-S178. doi: 10.1093/cid/ciy643.

  PMID: 30423039 BACKGROUND

• Ko HF, Tsui SS, Tse JW, Kwong WY, Chan OY, Wong GC. Improving the emergency department management of post-chemotherapy sepsis in haematological malignancy patients. Hong Kong Med J. 2015 Feb;21(1):10-5. doi: 10.12809/hkmj144280. Epub 2014 Oct 10.

  PMID: 25306894 BACKGROUND

• Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 Update. Crit Care Med. 2018 Jun;46(6):997-1000. doi: 10.1097/CCM.0000000000003119. No abstract available.

  PMID: 29767636 BACKGROUND

• Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA, Nastoupil LJ, Rajotte M, Rolston K, Strasfeld L, Flowers CR. Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol. 2018 May 10;36(14):1443-1453. doi: 10.1200/JCO.2017.77.6211. Epub 2018 Feb 20.

  PMID: 29461916 BACKGROUND

• Boxer L, Dale DC. Neutropenia: causes and consequences. Semin Hematol. 2002 Apr;39(2):75-81. doi: 10.1053/shem.2002.31911.

  PMID: 11957188 BACKGROUND

• Pizzo PA, Robichaud KJ, Wesley R, Commers JR. Fever in the pediatric and young adult patient with cancer. A prospective study of 1001 episodes. Medicine (Baltimore). 1982 May;61(3):153-65. doi: 10.1097/00005792-198205000-00003. No abstract available.

  PMID: 7078399 BACKGROUND

• Pasikhova Y, Ludlow S, Baluch A. Fever in Patients With Cancer. Cancer Control. 2017 Apr;24(2):193-197. doi: 10.1177/107327481702400212.

  PMID: 28441374 BACKGROUND

• Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006 May 15;106(10):2258-66. doi: 10.1002/cncr.21847.

  PMID: 16575919 BACKGROUND

• Caggiano V, Weiss RV, Rickert TS, Linde-Zwirble WT. Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer. 2005 May 1;103(9):1916-24. doi: 10.1002/cncr.20983.

  PMID: 15751024 BACKGROUND

• Klastersky J, Ameye L, Maertens J, Georgala A, Muanza F, Aoun M, Ferrant A, Rapoport B, Rolston K, Paesmans M. Bacteraemia in febrile neutropenic cancer patients. Int J Antimicrob Agents. 2007 Nov;30 Suppl 1:S51-9. doi: 10.1016/j.ijantimicag.2007.06.012. Epub 2007 Aug 8.

  PMID: 17689933 BACKGROUND

• Culakova E, Thota R, Poniewierski MS, Kuderer NM, Wogu AF, Dale DC, Crawford J, Lyman GH. Patterns of chemotherapy-associated toxicity and supportive care in US oncology practice: a nationwide prospective cohort study. Cancer Med. 2014 Apr;3(2):434-44. doi: 10.1002/cam4.200. Epub 2014 Feb 17.

  PMID: 24706592 BACKGROUND

• Weycker D, Li X, Edelsberg J, Barron R, Kartashov A, Xu H, Lyman GH. Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors. J Oncol Pract. 2015 Jan;11(1):47-54. doi: 10.1200/JOP.2014.001492. Epub 2014 Dec 9.

  PMID: 25491042 BACKGROUND

• Rainer TH, Lam RPK, Tsang TC, Wai AK, Leung SC, Leung RYY, Wong CKH, Gill H, Lam WWT, Wing Lok Chan W, Chi Kin Cheung A, Lau MT, Lee SF, Choi YF, Fong Lun Lee H, Mok KL, Lam HC, Lee SY, Ho Ting Yeung M, Hung IF. Antibiotic stewardship in suspected neutropenic fever (ASTERIC trial): a multicentre, type 1 hybrid effectiveness-implementation, stepped-wedge, randomised controlled trial study protocol. BMJ Open. 2025 Nov 24;15(11):e108010. doi: 10.1136/bmjopen-2025-108010.

  PMID: 41290295 DERIVED

MeSH Terms

Conditions

Febrile Neutropenia; Neoplasms; Carcinoma; Emergencies; Hematologic Neoplasms

Interventions

NF protocol

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site

Study Officials

• Professor RAINER Timothy Hudson, MBBCh

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy Hudson Professor Rainer, MBBCh

CONTACT

39176846; thrainer@hku.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: type 1 hybrid effectiveness-implementation, stepped-wedge, randomised controlled trial
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: BSc (Hons), MBBCh, MRCP (UK), FHKCEM, FHKAM, MD, FRCEM, FRCP, FIFEM

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 27, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 27, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)