Fast-track Blood Test for Suspected Fever by Deficiency of a Kind of White Blood Cells As Main Defense Against Infection

NCT05393505 | Unknown Phase 4

• 1 other identifier: CTC2178HKU1
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 1

Brief Summary

This is a comparative study for adult participants with cancer who are suspected to have neutropenic fever (or fever with low neutrophil count) in emergency department. Neutrophil is a kind of defensive white blood cell combating against infection, especially by bacteria and fungi. Low neutrophil can be part of the disease progress or secondary to some cancer treatment. These participants are at high risk of developing infection-related complications including death. Currently a dedicated clinical pathway has been in place in emergency department for suspected neutropenic fever, which offers fast-track medical consultation, blood tests and a very strong antibiotic (meropenem) as the first choice within 1 hour of registration. However, majority of such participants' neutrophil counts are not low. Most of them have no bacterial infection in the body, and have unremarkable short hospital stays. Early administration of meropenem in the majority of cases may be unnecessary and imposes risk of developing antibiotic resistance. This study attempts to answer the question, "In adult participants with cancer presenting to emergency department with suspected neutropenic fever, when compared with conventional treatment, can a new protocol guided by fast-track neutrophil count reduces prescription of meropenem?" Agreed participants will be randomly assigned to the conventional treatment group, or the new treatment group. For those who are assigned to the new treatment group, blood will be taken and sent to the hospital laboratory for urgent analysis of neutrophil count. Participants with proven low neutrophil counts will still receive meropenem, while those without low neutrophil counts will receive less strong antibiotic according to their clinical diagnoses, such as Augmentin. They will be followed up on the first 7 days, and then on the 14th, 30th, 90th, and 180th days after recruitment. Comparisons will be made to see how much less meropenem will be prescribed, and whether more serious adverse events will happen. The study is expected to take 37 months to complete. Duration of data collection, including the day of last follow up, is estimated to be 33 months.

Conditions

Neutropenic Fever

Keywords

febrile neutropenia; emergency department; cancer; adult; sepsis; randomized controlled trial; antibiotic stewardship; clinical laboratory services; chemotherapy; hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• Antibiotic stewardship as assessed by proportion of participants receiving Meropenem

  Proportion of participants in each group receiving Meropenem

  Up to 7 days post-randomisation

Secondary Outcomes (16)

• Clinically and/or microbiologically documented infections

  Up to 15 days post-randomisation

• Time to clinical improvement

  Up to 15 days post-randomisation

• Incidence of adverse events requiring emergency interventions

  Up to 15 days post-randomisation

• Rate of life-saving interventions

  Up to 15 days post-randomisation

• Length of hospital stay

  Up to 180 days post-randomisation

Study Arms (2)

Fast-tRack Absolute Neutrophil Count (FRANC) Protocol

EXPERIMENTAL

Patient's blood sample will be expedited for complete blood count with differentials. Intravenous antibiotic is given depending on absolute neutrophil count. If neutropenia is present, broad-spectrum antibiotic (meropenem 1 g or levofloxacin 500 mg) will be given after septic workup within 1 hour of registration in emergency department before transfer to wards. If absent, antibiotic according to "Hospital Authority Interhospital Multi-disciplinary Programme on Antimicrobial ChemoTherapy (IMPACT)" with reference to previous bacterial sensitivity pattern, or amoxiclav 1.2 g if not specified, will be given. Other interventions are given according to clinical needs. The regimen is continued until clinicians recommend an alternative antimicrobial based on clinical grounds, or detection of other pathogens which indicate another antimicrobial.

Drug: Meropenem Injection; Drug: Levofloxacin; Drug: Amoxicillin Clavulanate; Drug: Antibiotic

Standard of Care

ACTIVE COMPARATOR

The control group refers to the existing clinical pathway which guides management of adult patients with suspected NF in ED. Without information of absolute neutrophil count, Meropenem 1 g IV bolus (or Levofloxacin 500 mg IV infusion over 1 hour if Penicillin-allergic) will be given within 1 hour of ED registration after septic workup. Other interventions are given according to clinical needs. Subsequent treatment in wards will be determined by doctor's clinical judgement, on a personalised basis. Each patient will be assessed by a parent team member. There is no standardised antibiotic de-escalation protocol in place, but it is a usual practice to continue Meropenem or Levofloxacin injections until clinical improvement, rising ANC, and negative culture results. After that it will be replaced with an antibiotic with a narrower spectrum, such as oral Amoxiclav, before discharge.

Drug: Meropenem Injection; Drug: Levofloxacin

Interventions

Meropenem Injection DRUG

Given if patient has no known allergies at 1 g IV bolus within 1 hour of ED registration, then every 8 hours

Fast-tRack Absolute Neutrophil Count (FRANC) Protocol; Standard of Care

Levofloxacin DRUG

Given if patient is allergic to beta lactam at 500 g IV in 100 mL 0.9% sodium chloride solution, infused over 1 hour started within 1 hour of ED registration, then every 24 hours. If the patient can tolerate oral drugs, 500 mg daily after the first IV dose.

Fast-tRack Absolute Neutrophil Count (FRANC) Protocol; Standard of Care

Amoxicillin Clavulanate DRUG

Given if patient has no known allergies at 1.2 g IV bolus within 1 hour of ED registration, then every 8 hours. If the patient can tolerate oral drugs, 1 g twice daily after the first IV bolus.

Also known as: Augmentin

Fast-tRack Absolute Neutrophil Count (FRANC) Protocol

Antibiotic DRUG

Any antibiotic for empirical therapy of common infections as recommended by the fifth version of "Hospital Authority Interhospital Multi-disciplinary Programme on Antimicrobial ChemoTherapy (IMPACT)" guideline, with reference to previous bacterial sensitivity pattern

Also known as: IMPACT guideline

Fast-tRack Absolute Neutrophil Count (FRANC) Protocol

Eligibility Criteria

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

You may qualify if:

• Age criteria: 18 years old or above; AND
• Body temperature criteria: Tympanic temperature ≥ 38.3 degree Celsius (100.9 degree Fahrenheit) within 24 hours before emergency department registration; AND
• Chemotherapy timeframe criteria: Last chemotherapy or targeted therapy within 6 weeks for any solid tumor, or in any period following therapies against leukemia, lymphoma, myelodysplastic syndrome, aplastic anemia, multiple myeloma, or recipient of hematopoietic stem cell transplantation; AND
• Modified Early Warning Score (MEWS) ≤ 4

You may not qualify if:

• Unable to provide informed consent
• Previous enrolment to this trial within 180 days, or without current resolution of the first episode
• Enrolment to other interventional trials within 187 days
• Sepsis or septic shock
• Suspected central nervous system infection
• Severe desaturation (SpO2 \< 88% in room air for patients with chronic obstructive pulmonary disease, severe chest wall or spinal disease, neuromuscular disease, severe obesity, cystic fibrosis, bronchiectasis; or \< 94% in room air without)
• Currently on prophylactic antibiotic
• Any antibiotic treatment for \> 48 h within 1 week
• Known human immunodeficiency virus infection
• Primary humoral immunodeficiency
• Complement deficiency
• Asplenia
• Vulnerable subjects (illiterate, pregnancy, mentally incapacitated, impoverished, prisoner, subordinate or students of investigators, ethnic minorities)
• Research staff not available
• Unable to randomize within 1 hour of emergency department registration

Sponsors & Collaborators

• The University of Hong Kong: lead
• Queen Mary Hospital, Hong Kong: collaborator

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong

RECRUITING

Related Publications (23)

• 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

• 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

• 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

• Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966 Feb;64(2):328-40. doi: 10.7326/0003-4819-64-2-328. No abstract available.

  PMID: 5216294 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

• Ihbe-Heffinger A, Paessens BJ, von Schilling C, Shlaen M, Gottschalk N, Berger K, Bernard R, Kiechle M, Peschel C, Jacobs VR. Management of febrile neutropenia--a German prospective hospital cost analysis in lymphoproliferative disorders, non-small cell lung cancer, and primary breast cancer. Onkologie. 2011;34(5):241-6. doi: 10.1159/000327711. Epub 2011 Apr 26.

  PMID: 21577029 BACKGROUND

• Wang XJ, Wong M, Hsu LY, Chan A. Costs associated with febrile neutropenia in solid tumor and lymphoma patients - an observational study in Singapore. BMC Health Serv Res. 2014 Sep 24;14:434. doi: 10.1186/1472-6963-14-434.

  PMID: 25252614 BACKGROUND

• Wang XJ, Lopez SE, Chan A. Economic burden of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review. Crit Rev Oncol Hematol. 2015 May;94(2):201-12. doi: 10.1016/j.critrevonc.2014.12.011. Epub 2014 Dec 31.

  PMID: 25600838 BACKGROUND

• Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA, Nastoupil LJ, Rajotte M, Rolston KV, Strasfeld L, Flowers CR. Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. J Clin Oncol. 2018 Oct 20;36(30):3043-3054. doi: 10.1200/JCO.18.00374. Epub 2018 Sep 4.

  PMID: 30179565 BACKGROUND

• Kobayashi SD, Voyich JM, Burlak C, DeLeo FR. Neutrophils in the innate immune response. Arch Immunol Ther Exp (Warsz). 2005 Nov-Dec;53(6):505-17.

  PMID: 16407783 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

• 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

• Castagnola E, Mikulska M, Viscoli C. Prophylaxis and Empirical Therapy of Infection in Cancer Patients. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 2015:3395-3413.e2. doi: 10.1016/B978-1-4557-4801-3.00310-6. Epub 2014 Oct 31. PMCID: PMC7173426.

  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

• 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

• Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med. 2018 Jun;44(6):925-928. doi: 10.1007/s00134-018-5085-0. Epub 2018 Apr 19. No abstract available.

  PMID: 29675566 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

• 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

• Velasco E, Byington R, Martins CA, Schirmer M, Dias LM, Goncalves VM. Comparative study of clinical characteristics of neutropenic and non-neutropenic adult cancer patients with bloodstream infections. Eur J Clin Microbiol Infect Dis. 2006 Jan;25(1):1-7. doi: 10.1007/s10096-005-0077-8.

  PMID: 16424972 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

• So SN, Ong CW, Wong LY, Chung JY, Graham CA. Is the Modified Early Warning Score able to enhance clinical observation to detect deteriorating patients earlier in an Accident & Emergency Department? Australas Emerg Nurs J. 2015 Feb;18(1):24-32. doi: 10.1016/j.aenj.2014.12.001. Epub 2015 Jan 15.

  PMID: 25601429 BACKGROUND

Related Links

• National Institute for Health and Care Excellence: Guidance. Neutropenic Sepsis: Prevention and Management of Neutropenic Sepsis in Cancer Patients
• Reducing bacterial resistance with IMPACT - Interhospital Multi-disciplinary Programme on. Antimicrobial ChemoTherapy (version 5.0)

MeSH Terms

Conditions

Febrile Neutropenia; Emergencies; Neoplasms; Sepsis

Interventions

Meropenem; Levofloxacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Drug Combinations; Pharmaceutical Preparations; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Timothy Hudson Rainer, MBBCh; MRCP

  Department of Emergency Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy Hudson Rainer, MBBCh; MRCP

CONTACT

+852-93133096; thrainer@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-center, pragmatic, open-labelled, randomized, controlled trial with 1:1 parallel-group assignment, which aims to establish superiority in antibiotic stewardship.

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: May 26, 2022
• Study Start: October 24, 2022
• Primary Completion: March 14, 2025
• Study Completion: June 30, 2025
• Last Updated: December 6, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)