Prospective Study Evaluate the Timing of Empirical Treatment for Carbapenem-resistant Bacterials (CROEAT Study)

Official title

A Multi-center Single Arm Prospective Study in Patients of Hematological Malignancies Colonized With Carbapenem-resistant Bacterials to Evaluate the Timing of Empirical Antibiotic Treatment (CROEAT Study)

Overview

In this study, we will evaluate the feasibility and clinical outcomes of risk adaptive empirical therapy to cover carbapenem resistance gram negative bacteria (CRO) in patients with hematological malignancies colonized with CRO. Patients assessed by the clinician as being at high risk for CRO infection and requiring intravenous antibiotics covering CRO must meet the following conditions: 1. Positive active screening for CRO or past CRO infection or local prevalence of CRO (e.g.,CRO detection rate\>20% among recently hospitalized patients); 2. Presence of fever or other possible signs and symptoms of infection; 3. Neutropenia(ANC\<0.1×10\^9/L)expected to last for ≥7 days,and having any of the following: * Gastrointestinal mucositis/peri-anal infection/intestinal obstruction; * Shock or severe sepsis; * Respiratory failure:deoxygenated PaO2\<60 mmHg or requiring mechanical ventilation; * Disseminated intravascular coagulation; * Altered mental status or psychiatric abnormalities; * Congestive heart failure requiring treatment; * Arrhythmia requiring treatment; * Recurrence of fever shortly after cessation of or during empirical treatment with carbapenems (≤7 days). The endpoints of study include incidence of blood-stream infection by CRO, incidence of all causes mortality, incidences of clinical and microbiology response.

Detailed description

Neutropenic fever is common in patients with hematological malignancies undergoing chemotherapy or transplantation. Empirical antibiotics therapy is essential treatment principle. In China, recent evidence demonstrated that the carbapenem resistant gram negative bacteria was emerging as an important issue and CRO colonization was positive in about 10% of patients by rectal swab. In such group of patients, the empirical treatment of patients with neutropenic fever therapy remained as a challenge. In this study, we plan to evaluate the feasibility and clinical outcomes of risk adaptive empirical therapy to cover CRO in patients with hematological malignancies colonized with CRO.

Patients assessed by the clinician as being at high risk for CRO infection and requiring intravenous antibiotics covering CRO must meet the following conditions:

1. Positive active screening for CRO or past CRO infection or local prevalence of CRO (e.g.,CRO detection rate\>20% among recently hospitalized patients); 2. Presence of fever or other possible signs and symptoms of infection; 3. Neutropenia(ANC\<0.1×10\^9/L)expected to last for ≥7 days,and having any of the following:

* Gastrointestinal mucositis/peri-anal infection/intestinal obstruction;

* Shock or severe sepsis;

* Respiratory failure:deoxygenated PaO2\<60 mmHg or requiring mechanical ventilation;

* Disseminated intravascular coagulation;

* Altered mental status or psychiatric abnormalities;

* Congestive heart failure requiring treatment;

* Arrhythmia requiring treatment;

* Recurrence of fever shortly after cessation of or during empirical treatment with carbapenems (≤7 days).

The endpoints of study include incidence of blood-stream infection by CRO, incidence of all causes mortality, incidences of clinical and microbiology response.

Interventions

• Other Empirical treatment
  Empirical treatment to cover carbapenem-resistant enterobacterales

Primary outcome measures

• Incidence of overall mortality [Time frame: 14 days]

Secondary outcome measures (3)

• Incidence of documented CRE blood stream infection [Time frame: 30 days]
• Clinical response [Time frame: 14 days]
• microbiology response [Time frame: 14 days]

Eligibility criteria

Inclusion criteria

• Patients with hematological malignancies receiving hospital treatment such as chemotherapy/immunotherapy/hematopoietic stem cell transplantation;
• Those with a recent history of CRO colonization or who have been screened for CRO once a week continuously since admission;
• Patients assessed by the clinician as being at high risk for CRO infection and requiring intravenous antibiotics covering CRO must meet the following conditions:

• Positive active screening for CRO or past CRO infection or local prevalence of CRO (e.g.,CRO detection rate>20% among recently hospitalized patients);
• Presence of fever or other possible signs and symptoms of infection;
• Neutropenia(ANC<0.1×10\^9/L)expected to last for ≥7 days,and having any of the following:

• Gastrointestinal mucositis/peri-anal infection/intestinal obstruction;

• Shock or severe sepsis;

• Respiratory failure:deoxygenated PaO2<60 mmHg or requiring mechanical ventilation;

• Disseminated intravascular coagulation;

• Altered mental status or psychiatric abnormalities;

• Congestive heart failure requiring treatment;

• Arrhythmia requiring treatment;

• Recurrence of fever shortly after cessation of or during empirical treatment with carbapenems (≤7 days).
• The patient or their legal guardian has signed the informed consent form.

Exclusion criteria

• Pregnant or breastfeeding women;
• Individuals who are expected to die within 14 days of hospitalization or have an expected hospital stay of less than 7 days;
• Any conditions that the investigator believes may increase the risk to the patient;
• Severe psychological or psychiatric disorders with poor estimated compliance;
• The presence of any other conditions that the investigator deems unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Rui Jin Hospital — Shanghai

Identifiers

NCT: NCT07047352 · RJH-BMT-2403

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗