고위험 열성 호중구감소증 환자에서의 항생제 투여 기간과 결과 (PERaSTrA)
2026년 9월 23일 업데이트: Valeria Cento
고위험 혈액학적 환자에서의 세균혈증성 발열성 호중구감소증의 적절한 관리. 항생제 투여 기간, 결과 및 내성 프로필 간의 관계
The goal of this clinical trial is to learn if a personalized duration of antibiotic therapy, based on clinical stability, is as effective as a standard duration of at least 10 days in hospitalized patients with hematologic malignancies (such as leukemia or lymphoma) who develop febrile neutropenia and Gram-negative bacteraemia.
The main questions it aims to answer are:
- Can a personalized antibiotic duration increase the number of days free from anti-Gram-negative therapy within 28 days without compromising patient safety?
- How does the duration of antibiotic therapy (short vs. prolonged) affect the rate and modality of gut microbiota reconstitution?
Researchers will compare:
- Group A (Personalized Duration): Antibiotics are stopped after the patient maintains clinical stability (no fever and stable vital signs) for 72 consecutive hours.
- Group B (Standard of Care): Antibiotics are continued for a standard duration, typically at least 10 days, based on current clinical surveys and physician decision.
Participants will:
- Be randomized to receive either the personalized or the standard duration of antibiotic therapy once a Gram-negative infection is confirmed in the blood.
- Be monitored for 28 days to assess for new fever episodes, recurrence of infection, and overall survival.
- If participating in the microbiological sub-study, provide biological samples (blood, feces, and rectal swabs) at specific time points (at the onset of fever, at the end of treatment, and at day 28).
- Undergo specialized laboratory testing (Whole Metagenomic Sequencing) on the collected samples to evaluate the evolution of their intestinal and blood microbiota and the presence of antibiotic-resistant genes.
연구 개요
상태
상태
모병
정황
정황
개입 / 치료
개입 / 치료
상세 설명
This is a multicenter, open-label, randomized controlled trial. Upon confirmation of Gram-negative bacteraemia, eligible patients are randomized 1:1 to one of two treatment strategies:
- Experimental Arm (Personalized Duration): Antibiotic therapy is discontinued once the patient achieves and maintains clinical stability for 72 consecutive hours. Clinical stability is defined as apyrexia (Tc < 38°C) for at least 48 hours and a stable or improving qSOFA score.
- Control Arm (Standard of Care): Antibiotic therapy duration follows local clinical practice, with a suggested minimum duration of 10 days, consistent with current European and Asian hematological guidelines.
In parallel, a prospective observational microbiological sub-study will utilize Shotgun Metagenomic Next-Generation Sequencing (mNGS) to analyze the evolution of the intestinal and blood microbiota. The goal is to compare the rate of MDR organism colonization and the reconstitution of the healthy microbiome between the two antibiotic duration strategies.
All participants will undergo clinical monitoring until day 28. For those enrolled in the sub-study, biological samples (stool, rectal swabs, and blood) will be collected at baseline (V1), at the end of treatment (V4), and at the end of the study (V5). These samples will be analyzed to identify clinically significant bacteria and antibiotic-resistance genes.
연구 유형
연구 유형
중재적
등록 (추정된)
등록
172
단계
단계
- 해당 없음
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
연구 연락처
- 이름: Valeria Cento, MD, PhD
- 전화번호: 0282243166
- 이메일: valeria.cento@hunimed.eu
연구 연락처 백업
- 이름: Michele Bartoletti, MD, PhD
- 전화번호: 0282243568
- 이메일: michele.bartoletti@hunimed.eu
연구 장소
-
-
Milan
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Rozzano, Milan, 이탈리아, 20089
- 모병
- Microbiology and Virology - IRCCS Humanitas Research Hospital
-
연락하다:
- Valeria Cento, MD, PhD
- 전화번호: 0282243166
- 이메일: valeria.cento@hunimed.eu
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Diagnosed with a hematologic malignancy that is candidate for treatment with chemotherapy or bone marrow transplantation or chimeric antigen receptor T cell therapy (CAR-T)
- Diagnosis of febrile neutropenia defined according to the guidelines of the Infectious Disease Society of America, IDSA; ref: Freifeld, A.G., et al., 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. 52(4): p. e56-93.) as: Fever: single record of oral temperature >=38.3°C or a temperature >=38.0°C sustained over a period of one hour; Neutropenia: absolute neutrophil count < 1000 cells/microL; Expected duration of neutropenia >= 7 days
- Diagnosis of bacteraemia defined by positive blood cultures (at least 1 vial positive for a non-contaminating microorganism)
- Isolation of Gram-Negative species
Exclusion Criteria:
- Contextual diagnosis of pneumonia
- Contextual diagnosis of intra-abdominal infection, in particular: neutropenic enterocolitis/typhlitis or biliary tract infection
- Persistently positive blood cultures at randomization
- Any condition that endangers the safety of the patient based on the judgment of the treating physician
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
2
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
활성 비교기: Standard of Care
Standard of care antibiotic therapy with a suggested minimum duration of 10 days. |
This intervention follows the standard clinical practice for treating Gram-negative bacteraemia in hematological patients. The duration of therapy is not fixed by a stability-driven rule but is based on the treating physician's decision, with a suggested minimum of 10 days.
다른 이름들:
|
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실험적: Personalized Duration
Patients in this arm will receive antibiotic therapy for a duration guided by clinical stability. Antibiotics will be discontinued after 72 consecutive hours of clinical stability, defined as apyrexia (Tc < 38°C) for at least 48 hours and stable or improved qSOFA score. |
A therapeutic strategy where the duration of antibiotic treatment for Gram-negative bacteraemia is determined by the achievement of clinical stability (defined as apyrexia for 48h and stable/improved qSOFA score) maintained for 72 consecutive hours
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Days Free from Anti-Gram-Negative Antibiotic Therapy within 28 days
기간: From the date of index blood culture collection (Day 0) up to Day 28
|
Number of days that the participant is alive and free from any anti-Gram-negative antibiotic therapy, calculated from the date of the index blood culture collection (onset of infection) up to Day 28. Antibiotics active exclusively on Gram-positive bacteria (e.g., glycopeptides, daptomycin) and fluoroquinolone prophylaxis are excluded from this calculation. |
From the date of index blood culture collection (Day 0) up to Day 28
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Incidence of New Fever Episodes
기간: From the end of antibiotic therapy up to Day 28
|
Number of participants experiencing a new episode of fever (Tc ≥ 38.3°C) occurring after a period of apyrexia of at least 72 hours |
From the end of antibiotic therapy up to Day 28
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28-day All-cause Mortality
기간: Up to Day 28
|
Number of participants who died from any cause within 28 days from the onset of the index infection (date of first positive blood culture) |
Up to Day 28
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Relapse of Bloodstream Infection (BSI) by the Same Pathogen
기간: From the end of antibiotic therapy up to Day 28
|
Number of participants with a new positive blood culture for the same Gram-negative pathogen identified in the index episode |
From the end of antibiotic therapy up to Day 28
|
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Recurrent BSI by Gram-negative Bacteria
기간: From the end of antibiotic therapy up to Day 28
|
Number of participants experiencing a new episode of bloodstream infection caused by any Gram-negative bacteria different from the index pathogen |
From the end of antibiotic therapy up to Day 28
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Emergence of Multi-Drug Resistant Organisms (MDRO)
기간: Within 90 days from the index blood culture collection
|
Number of participants with isolation of a new MDRO from recurrent positive blood cultures, or evidence of a worsened resistance profile compared to the index isolate |
Within 90 days from the index blood culture collection
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Incidence of Clostridioides difficile Infection (CDI)
기간: Up to Day 28
|
Number of participants with a laboratory-confirmed diagnosis of Clostridioides difficile infection |
Up to Day 28
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Incidence of Antibiotic-Related Adverse Events
기간: Up to Day 28
|
Number of participants experiencing adverse events (AE) judged by the investigator to be related to the antibiotic therapy (e.g., allergic reactions, renal toxicity) |
Up to Day 28
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
협력자
협력자
수사관
수사관
- 수석 연구원: Valeria Cento, MD, PhD, Humanitas University
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
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- Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
- Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, Weber D, Hashimoto D, Slingerland AE, Slingerland JB, Maloy M, Clurman AG, Stein-Thoeringer CK, Markey KA, Docampo MD, Burgos da Silva M, Khan N, Gessner A, Messina JA, Romero K, Lew MV, Bush A, Bohannon L, Brereton DG, Fontana E, Amoretti LA, Wright RJ, Armijo GK, Shono Y, Sanchez-Escamilla M, Castillo Flores N, Alarcon Tomas A, Lin RJ, Yanez San Segundo L, Shah GL, Cho C, Scordo M, Politikos I, Hayasaka K, Hasegawa Y, Gyurkocza B, Ponce DM, Barker JN, Perales MA, Giralt SA, Jenq RR, Teshima T, Chao NJ, Holler E, Xavier JB, Pamer EG, van den Brink MRM. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med. 2020 Feb 27;382(9):822-834. doi: 10.1056/NEJMoa1900623.
- Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M; Bacteremia Duration Study Group. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis. 2019 Sep 13;69(7):1091-1098. doi: 10.1093/cid/ciy1054.
- 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.
- Zimmer AJ, Freifeld AG. Optimal Management of Neutropenic Fever in Patients With Cancer. J Oncol Pract. 2019 Jan;15(1):19-24. doi: 10.1200/JOP.18.00269.
- Taur Y, Coyte K, Schluter J, Robilotti E, Figueroa C, Gjonbalaj M, Littmann ER, Ling L, Miller L, Gyaltshen Y, Fontana E, Morjaria S, Gyurkocza B, Perales MA, Castro-Malaspina H, Tamari R, Ponce D, Koehne G, Barker J, Jakubowski A, Papadopoulos E, Dahi P, Sauter C, Shaffer B, Young JW, Peled J, Meagher RC, Jenq RR, van den Brink MRM, Giralt SA, Pamer EG, Xavier JB. Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant. Sci Transl Med. 2018 Sep 26;10(460):eaap9489. doi: 10.1126/scitranslmed.aap9489.
- Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Jul 1;49(1):1-45. doi: 10.1086/599376.
- von Dach E, Albrich WC, Brunel AS, Prendki V, Cuvelier C, Flury D, Gayet-Ageron A, Huttner B, Kohler P, Lemmenmeier E, McCallin S, Rossel A, Harbarth S, Kaiser L, Bochud PY, Huttner A. Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial. JAMA. 2020 Jun 2;323(21):2160-2169. doi: 10.1001/jama.2020.6348.
- Giannella M, Pascale R, Toschi A, Ferraro G, Graziano E, Furii F, Bartoletti M, Tedeschi S, Ambretti S, Lewis RE, Viale P. Treatment duration for Escherichia coli bloodstream infection and outcomes: retrospective single-centre study. Clin Microbiol Infect. 2018 Oct;24(10):1077-1083. doi: 10.1016/j.cmi.2018.01.013. Epub 2018 Jan 31.
- Stern A, Carrara E, Bitterman R, Yahav D, Leibovici L, Paul M. Early discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution in people with cancer. Cochrane Database Syst Rev. 2019 Jan 3;1(1):CD012184. doi: 10.1002/14651858.CD012184.pub2.
- Van de Wyngaert Z, Berthon C, Debarri H, Bories C, Bonnet S, Nudel M, Carpentier B, Legrand C, Barbieux S, Chauvet P, Simonnet A, Willaume A, Bossard JB, Renaud L, Wattebled KJ, Escure G, Branche N, Arib I, Titecat M, Quesnel B, Alfandari S. Discontinuation of antimicrobial therapy in adult neutropenic haematology patients: A prospective cohort. Int J Antimicrob Agents. 2019 Jun;53(6):781-788. doi: 10.1016/j.ijantimicag.2019.02.020. Epub 2019 Mar 2.
- Robilotti E, Holubar M, Seo SK, Deresinski S. Feasibility and applicability of antimicrobial stewardship in immunocompromised patients. Curr Opin Infect Dis. 2017 Aug;30(4):346-353. doi: 10.1097/QCO.0000000000000380.
- Trecarichi EM, Pagano L, Martino B, Candoni A, Di Blasi R, Nadali G, Fianchi L, Delia M, Sica S, Perriello V, Busca A, Aversa F, Fanci R, Melillo L, Lessi F, Del Principe MI, Cattaneo C, Tumbarello M; HaematologicMalignancies Associated Bloodstream Infections Surveillance (HEMABIS) registry - Sorveglianza Epidemiologica Infezioni Funginein Emopatie Maligne(SEIFEM) group, Italy. Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey. Am J Hematol. 2016 Nov;91(11):1076-1081. doi: 10.1002/ajh.24489. Epub 2016 Jul 29.
- Gustinetti G, Mikulska M. Bloodstream infections in neutropenic cancer patients: A practical update. Virulence. 2016 Apr 2;7(3):280-97. doi: 10.1080/21505594.2016.1156821.
- Mikulska M, Del Bono V, Bruzzi P, Raiola AM, Gualandi F, Van Lint MT, Bacigalupo A, Viscoli C. Mortality after bloodstream infections in allogeneic haematopoietic stem cell transplant (HSCT) recipients. Infection. 2012 Jun;40(3):271-8. doi: 10.1007/s15010-011-0229-y. Epub 2011 Dec 21.
- Girmenia C, Bertaina A, Piciocchi A, Perruccio K, Algarotti A, Busca A, Cattaneo C, Raiola AM, Guidi S, Iori AP, Candoni A, Irrera G, Milone G, Marcacci G, Scime R, Musso M, Cudillo L, Sica S, Castagna L, Corradini P, Marchesi F, Pastore D, Alessandrino EP, Annaloro C, Ciceri F, Santarone S, Nassi L, Farina C, Viscoli C, Rossolini GM, Bonifazi F, Rambaldi A; Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and Associazione Microbiologi Clinici Italiani (AMCLI). Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey. Clin Infect Dis. 2017 Nov 13;65(11):1884-1896. doi: 10.1093/cid/cix690.
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- Klastersky J. Management of fever in neutropenic patients with different risks of complications. Clin Infect Dis. 2004 Jul 15;39 Suppl 1:S32-7. doi: 10.1086/383050.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
연구 시작
2026년 2월 2일
기본 완료 (추정된)
기본 완료
2028년 2월 28일
연구 완료 (추정된)
연구 완료
2028년 11월 30일
연구 등록 날짜
최초 제출
최초 제출
2026년 1월 20일
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
2026년 1월 20일
처음 게시됨 (실제)
처음 게시됨
2026년 1월 28일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
2026년 9월 24일
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
2026년 9월 23일
마지막으로 확인됨
마지막으로 확인됨
2026년 9월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- PERaSTrA
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .