Other Infectious DiseasesPhase 2NCT03485950
Comparative Study To Determine The Efficacy, Safety, And Tolerability Of Ceftolozane-Tazobactam
A Phase 2 study testing Cefepime, Ceftolozane and Laboratory Biomarker Analysis in people with Other Infectious Diseases, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if the study drug ceftolozane-tazobactam is more effective in controlling febrile neutropenia (fever and low white blood cell counts) than using approved antibiotics in patients with cancer. The safety of ceftolozane-tazobactam will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Other Infectious Diseases
- What is being tested?
- Cefepime, Ceftolozane and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2018to 16 Feb 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has provided written informed consent, and has the willingness and ability to comply with all study procedures
- Patients with neutropenic fever who have existing malignancy or have undergone hematopoietic stem cell transplantation; neutropenic fever is defined as the presence of neutropenia defined by: 1) absolute neutrophil count (ANC) < 500 cells/mm^3 or has an ANC that is expected to decrease to < 500 cells/mm^3 within 48 hours of trial entry and fever defined as: 2) single oral temperature measurement of > 101 degree Fahrenheit (F) (38.3 degree Celsius [C]) or a temperature of > 100.4 degree F (38.0 degree C) sustained over a 1-hour period
- Requires hospitalization for IV empiric antibiotic therapy
- If female: not breastfeeding; agrees to not attempt to become pregnant during the study; is surgically sterile or at least 2-years postmenopausal, or if of childbearing potential, has negative screening serum pregnancy test (if serum pregnancy test results are not available at the time of enrollment, a negative urine pregnancy test is required within 24 hours.); if of childbearing potential (including being < 2 years postmenopausal), is willing to practice sexual abstinence or use an effective dual form of contraception with her partner (eg, 2 barrier methods, barrier method plus hormonal method) during treatment and for ≥ 28 days after the last dose of any study therapy (IV or oral)
Who cannot join
- History of any hypersensitivity or allergic reaction to any cephalosporin antibiotic or tazobactam
- Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or blood product administration)
- Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with pneumonia) that justifies adding additional empiric antimicrobial therapy (eg, antifungals)
- Confirmed viral infection that justifies adding additional empiric antiviral therapy (eg, ganciclovir, foscarnet)
- Known acute viral hepatitis
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 5 times the upper limit of normal (x ULN); patients with values > 3 x ULN and < 5 x ULN are eligible if the value is acute and directly related to the infectious process being treated
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- Total bilirubin > 3 x ULN unless isolated hyperbilirubinemia is directly related to the acute infection or due to known Gilbert disease; manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy
- Known to be human immunodeficiency virus positive
- Severely impaired renal function, defined as creatinine clearance (CrCl) =< 30 mL/min estimated by the Cockcroft-Gault formula
- Expected requirement for hemodialysis while on study therapy
- Received > 24 hours of IV antibacterial therapy (with study drugs) within 72 hours of the initiation of inpatient IV study drug for treatment of suspected infection; antibiotic prophylaxis and oral antibiotics is allowed; prophylactic use of antiviral or antifungal medication is permitted
- Requirement for any non-study potentially effective concomitant systemic antibacterial therapy
- Past or current history of epilepsy or seizure disorder; exception: well-documented febrile seizure of childhood
- Evidence of immediately life-threatening disease, progressively fatal disease, or life expectancy of 3 months or less (eg, moribund or with shock unresponsive to fluid replacement)
- Unable or unwilling to adhere to the study-specified procedures and restrictions
- Any condition that would make the patient, in the opinion of the investigator, unsuitable for the study (eg, would place a patient at risk or compromise the quality of the data
- Participation in any other ongoing ceftolozane/tazobactam trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Investigator Initiated, Phase II Single-Center, Randomized, Open-Label, Prospective, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftolozane-Tazobactam Plus Vancomycin, Linezolid Versus Standard of Care Plus Vancomycin, Linezolid as Empiric Therapy in Febrile Neutropenic Adults With Cancer
The goal of this clinical research study is to learn if the study drug ceftolozane-tazobactam is more effective in controlling febrile neutropenia (fever and low white blood cell counts) than using approved antibiotics in patients with cancer. The safety of ceftolozane-tazobactam will also be studied.
This is an investigational study. Ceftolozane-tazobactam is FDA approved and commercially available to treat certain types of infections. It is not approved for the treatment of febrile neutropenia, either by itself or in combination with other antibiotics. Its use to treat febrile neutropenia is investigational.
Read more
All other antibiotics given on this study are FDA approved and commercially available for the treatment of infections. However, only cefepime is specifically FDA approved to treat febrile neutropenia. The study doctor can explain how the study drugs are designed to work.
Up to 100 participants will take part in this study. All will be enrolled at MD Anderson.
Read the detailed description
Study Groups and Study Drug Administration:
If participant is found to be eligible to take part in this study and participant agrees, participant will be randomly assigned (as in the flip of a coin) to either receive either the study drug (Group 1) or a standard treatment antibiotic (Group 2). This is done because no one knows if one study group is better, the same, or worse than the other group. Both participant and the study doctor will know what participant is receiving.
If participant is in Group 1, participant will receive ceftolozane-tazobactam by vein over 1 hour every 8 hours.
If participant is in Group 2, participant will receive a standard treatment antibiotic. This may include one of the following 3 options:
cefepime by vein over about 30 minutes every 8 hours. meropenem by vein over about 30 minutes every 8 hours. piperacillin/tazobactam by vein over about 1 hour every 6 hours.
Participant will receive the study drugs by vein for at least 3 days. After 3 days, if the study doctor thinks it is in participant's best interest and participant is eligible, participant may switch to receiving a different antibiotic either by mouth or by vein. The study doctor will tell participant more about what antibiotic participant may begin to receive, how it is administered, and its possible risks. If participant begins taking the study drugs by mouth, the study doctor or study staff will tell participant how and when to take each drug.
If the doctor thinks it is needed, participant will be given additional standard drugs to help control the infection. Participant may ask the study staff for information about how the drugs are given and their risks.
Length of Study:
Participant may receive the study drugs for up to 14 days. Participant will no longer be able to receive the study drugs if the disease gets worse, if intolerable side effects occur, if participant needs treatment that is not allowed on this study, or if participant is unable to follow study directions.
Participation on this study will be over after the late follow-up visit.
Study Visits:
Participant will have the following tests/procedures while participant is in the hospital. If participant begins to take the study drugs by mouth, participant will no longer have these study visits.
Each day for up to 2 weeks, if the doctor thinks it is needed, blood (about 1 tablespoon) or urine will be collected for routine tests.
Every 2 days for up to 2 weeks, blood (about 1 tablespoon) will be drawn to check for infection. Participant will stop having these blood draws when there is no longer a sign of infection and participant does not have a fever.
Twice each week for up to 2 weeks, participant will have a physical exam.
Follow-Up:
Within 72 hours (3 days) after participant's last dose of participant's assigned study treatment and before starting the second antibiotic therapy (if applicable):
Participant will have a physical exam. Blood (about 1 tablespoon) and urine will be collected for routine tests. If participant tested positive for infection at the beginning of the study, blood (about 1 tablespoon) will be drawn to check for infection. The study doctor will tell participant if participant will have this blood draw.
About 21-28 days (3-4 weeks) after participant's first dose of study drug, participant will return to MD Anderson for the following tests/procedures:
Participant will have a physical exam. If participant tested positive for infection at the beginning of the study, blood (about 1 tablespoon) will be drawn to check for infection. The study doctor will tell participant if participant will have this blood draw.
If participant can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test.
About 35-42 days (5-6 weeks) after participant's first dose of study drug, a member of the study staff will call participant to ask about any new drugs participant may have started and if participant is having any side effects. If participant is called, it should last about 10 minutes. If the doctor or study staff thinks it is needed, participant will be asked to come back to the clinic for the following tests/procedures:
Participant will have a physical exam. If the doctor thinks it is needed, blood (about 1 tablespoon) will be drawn to check for infection.
At any of these follow-up visits, if participant's doctor thinks it is needed, participant will have a chest x-ray or CT scan to check participant's lungs.
- Conditions
- Other Infectious Diseases
- Being tested
- Cefepime, Ceftolozane, Laboratory Biomarker Analysis, Meropenem, Piperacillin-Tazobactam
- Keywords
- Other infectious diseases, Febrile neutropenic adults with cancer, Ceftolozane-Tazobactam, Cefepime, Meropenem, Piperacillin/Tazobactam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CefepimeDrug
Given IV
CeftolozaneDrug
Also called CXA-101
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
MeropenemDrug
Also called Meropenem Trihydrate, Merrem I.V., SM-7338
Given IV
Piperacillin-TazobactamDrug
Also called PIPER/TAZO, Piperacillin/Tazobactam, Zosyn
Given IV
TazobactamDrug
Also called YTR-830H
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Group I (ceftolozane-tazobactam) | Experimental | Participants receive ceftolozane-tazobactam IV over 1 hour every 8 hours for up to 14 days in the absence of disease progression or unacceptable toxicity. After at least 3 days, participants may switch to different PO or IV antibiotics at the discretion of the study doctor. Receives: Drug: Ceftolozane; Other: Laboratory Biomarker Analysis; Drug: Tazobactam |
| Group II (standard of care antibiotic treatment) | Active comparator | Participants receive standard of care antibiotic treatment consisting of either cefepime IV over 30 minutes every 8 hours, meropenem IV over 30 minutes every 8 hours, or piperacillin-tazobactam IV over 1 hour every 6 hours for up to 14 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cefepime; Other: Laboratory Biomarker Analysis; Drug: Meropenem; Drug: Piperacillin-Tazobactam; Drug: Tazobactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Favorable Clinical Response at End of Inpatient Intravenous Therapy (EOIV)
Resolution of all acute signs and symptoms of the primary infection or improvement to such an extent that no additional antibacterial therapy is required (ie, except for protocol-allowed adjunctive therapies and/or oral or IV switch) and such that no more than 14 days of total antibacterial therapy is required.
Measured: Within 72 hours after administration of the last dose of inpatient IV study drug
Secondary outcomes (23)
Number of Participants With Favorable Clinical Response in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set at EOIV.
The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: Within 72 hours after administration of the last dose of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the Clinically Evaluable (CE) Analysis Set at EOIV.
The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: Within 72 hours after administration of the last dose of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the MITT Analysis Set at TOC
The secondary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the MITT Analysis Set at Late Follow-Up (LFU)
The secondary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the mMITT Analysis Set at Test of Cure (TOC)
The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 21 to 28 days after the start of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the mMITT Analysis Set at Late Follow-Up (LFU)
The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the CE Analysis Set at TOC
The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the CE Analysis Set at LFU.
The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the ME Analysis Set at EOIV.
The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: Within 72 hours after administration of the last dose of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the ME Analysis Set at TOC
The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 21 to 28 days after the start of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the ME Analysis Set at LFU.
The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Favorable Microbiological Response in the mMITT Analysis Set at EOIV.
The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: Within 72 hours after administration of the last dose of inpatient IV study drug
Favorable Microbiological Response in the mMITT Analysis Set at TOC.
The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Favorable Microbiological Response in the mMITT Analysis Set at LFU.
The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 35 to 42 days after the start of inpatient IV study drug.
Number of Participants With Favorable Microbiological Response in the ME Analysis Set at EOIV.
The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: Within 72 hours after administration of the last dose of inpatient IV study drug
Number of Participants With Favorable Microbiological Response in the ME Analysis Set at TOC.
The secondary efficacy outcome is favorable microbiological response of the patients in the ME (Microbiologically Evaluable) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Favorable Microbiological Response in the ME Analysis Set at LFU
The secondary efficacy outcome is favorable microbiological response of the patients in the ME (Microbiologically Evaluable) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
Measured: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Infection-related Mortality in the MITT Analysis Set at TOC
The secondary efficacy outcome is infection-related mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC).
Measured: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Infection-related Mortality in the MITT Analysis Set at LFU
The secondary efficacy outcome is infection-related mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at late follow-up (LFU).
Measured: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Infection-related Mortality the mMITT Analysis Set at TOC
The secondary efficacy outcome is infection-related mortality of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC).
Measured: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Infection-related Mortality in the mMITT Analysis Set at LFU.
The secondary efficacy outcome is infection-related mortality of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU).
Measured: 35 to 42 days after the start of inpatient IV study drug
30 Day All-cause Mortality in the MITT Analysis Set
The secondary efficacy outcome is all-cause mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set, which is mortality within 30 days after the last dose of inpatient IV study drug.
Measured: 30 days after the last dose of inpatient IV study drug
30 Day All-cause Mortality in the mMITT Analysis Set
The secondary efficacy outcome is all-cause mortality of the patients in the mMITT (microbiological Modified Intent-To-Treat) Analysis Set, which is mortality within 30 days after the last dose of inpatient IV study drug.
Measured: 30 days after the last dose of inpatient IV study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2018
- Study start16 May 2018
- Primary completion1 May 2021
- Study completion16 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Other Infectious DiseasesStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Issam I Raad, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03485950
- Sponsor's protocol ID
- 2017-0729
- Other IDs
- NCI-2018-00755, 2017-0729
- Status last verified
- Mar 2022
- First submitted
- 26 Mar 2018
- Last updated
- 15 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Chaftari AM, Hachem R, Malek AE, Mulanovich VE, Szvalb AD, Jiang Y, Yuan Y, Ali S, Deeba R, Chaftari P, Raad I. A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients With Hematological Malignancies. Open Forum Infect Dis. 2022 Feb 14;9(6):ofac079. doi: 10.1093/ofid/ofac079. eCollection 2022 Jun.
PubMed 35663286
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator Initiated, Phase II Single-Center, Randomized, Open-Label, Prospective, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftolozane-Tazobactam Plus Vancomycin, Linezolid Versus Standard of Care Plus Vancomycin, Linezolid as Empiric Therapy in Febrile Neutropenic Adults With Cancer
- ClinicalTrials.gov ID
- NCT03485950
- Acronym / sponsor ID
- 2017-0729
- Conditions
- Other Infectious Diseases
- Keywords
- Other infectious diseases, Febrile neutropenic adults with cancer, Ceftolozane-Tazobactam, Cefepime, Meropenem, Piperacillin/Tazobactam
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, National Cancer Institute (NCI)
- Study start
- 16 May 2018 (actual)
- Primary completion
- 1 May 2021 (actual)
- Study completion
- 16 Feb 2022 (actual)
- First posted
- 3 Apr 2018 (actual)
- Results
- Posted 20 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if the study drug ceftolozane-tazobactam is more effective in controlling febrile neutropenia (fever and low white blood cell counts) than using approved antibiotics in patients with cancer. The safety of ceftolozane-tazobactam will also be studied.
This is an investigational study. Ceftolozane-tazobactam is FDA approved and commercially available to treat certain types of infections. It is not approved for the treatment of febrile neutropenia, either by itself or in combination with other antibiotics. Its use to treat febrile neutropenia is investigational.
All other antibiotics given on this study are FDA approved and commercially available for the treatment of infections. However, only cefepime is specifically FDA approved to treat febrile neutropenia. The study doctor can explain how the study drugs are designed to work.
Up to 100 participants will take part in this study. All will be enrolled at MD Anderson.
Detailed description
Study Groups and Study Drug Administration:
If participant is found to be eligible to take part in this study and participant agrees, participant will be randomly assigned (as in the flip of a coin) to either receive either the study drug (Group 1) or a standard treatment antibiotic (Group 2). This is done because no one knows if one study group is better, the same, or worse than the other group. Both participant and the study doctor will know what participant is receiving.
If participant is in Group 1, participant will receive ceftolozane-tazobactam by vein over 1 hour every 8 hours.
If participant is in Group 2, participant will receive a standard treatment antibiotic. This may include one of the following 3 options:
cefepime by vein over about 30 minutes every 8 hours. meropenem by vein over about 30 minutes every 8 hours. piperacillin/tazobactam by vein over about 1 hour every 6 hours.
Participant will receive the study drugs by vein for at least 3 days. After 3 days, if the study doctor thinks it is in participant's best interest and participant is eligible, participant may switch to receiving a different antibiotic either by mouth or by vein. The study doctor will tell participant more about what antibiotic participant may begin to receive, how it is administered, and its possible risks. If participant begins taking the study drugs by mouth, the study doctor or study staff will tell participant how and when to take each drug.
If the doctor thinks it is needed, participant will be given additional standard drugs to help control the infection. Participant may ask the study staff for information about how the drugs are given and their risks.
Length of Study:
Participant may receive the study drugs for up to 14 days. Participant will no longer be able to receive the study drugs if the disease gets worse, if intolerable side effects occur, if participant needs treatment that is not allowed on this study, or if participant is unable to follow study directions.
Participation on this study will be over after the late follow-up visit.
Study Visits:
Participant will have the following tests/procedures while participant is in the hospital. If participant begins to take the study drugs by mouth, participant will no longer have these study visits.
Each day for up to 2 weeks, if the doctor thinks it is needed, blood (about 1 tablespoon) or urine will be collected for routine tests.
Every 2 days for up to 2 weeks, blood (about 1 tablespoon) will be drawn to check for infection. Participant will stop having these blood draws when there is no longer a sign of infection and participant does not have a fever.
Twice each week for up to 2 weeks, participant will have a physical exam.
Follow-Up:
Within 72 hours (3 days) after participant's last dose of participant's assigned study treatment and before starting the second antibiotic therapy (if applicable):
Participant will have a physical exam. Blood (about 1 tablespoon) and urine will be collected for routine tests. If participant tested positive for infection at the beginning of the study, blood (about 1 tablespoon) will be drawn to check for infection. The study doctor will tell participant if participant will have this blood draw.
About 21-28 days (3-4 weeks) after participant's first dose of study drug, participant will return to MD Anderson for the following tests/procedures:
Participant will have a physical exam. If participant tested positive for infection at the beginning of the study, blood (about 1 tablespoon) will be drawn to check for infection. The study doctor will tell participant if participant will have this blood draw.
If participant can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test.
About 35-42 days (5-6 weeks) after participant's first dose of study drug, a member of the study staff will call participant to ask about any new drugs participant may have started and if participant is having any side effects. If participant is called, it should last about 10 minutes. If the doctor or study staff thinks it is needed, participant will be asked to come back to the clinic for the following tests/procedures:
Participant will have a physical exam. If the doctor thinks it is needed, blood (about 1 tablespoon) will be drawn to check for infection.
At any of these follow-up visits, if participant's doctor thinks it is needed, participant will have a chest x-ray or CT scan to check participant's lungs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I (ceftolozane-tazobactam) | Experimental | Drug: Ceftolozane, Other: Laboratory Biomarker Analysis, Drug: TazobactamParticipants receive ceftolozane-tazobactam IV over 1 hour every 8 hours for up to 14 days in the absence of disease progression or unacceptable toxicity. After at least 3 days, participants may switch to different PO or IV antibiotics at the discretion of the study doctor. |
| Group II (standard of care antibiotic treatment) | Active comparator | Drug: Cefepime, Other: Laboratory Biomarker Analysis, Drug: Meropenem, Drug: Piperacillin-Tazobactam, Drug: TazobactamParticipants receive standard of care antibiotic treatment consisting of either cefepime IV over 30 minutes every 8 hours, meropenem IV over 30 minutes every 8 hours, or piperacillin-tazobactam IV over 1 hour every 6 hours for up to 14 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Has provided written informed consent, and has the willingness and ability to comply with all study procedures
- Patients with neutropenic fever who have existing malignancy or have undergone hematopoietic stem cell transplantation; neutropenic fever is defined as the presence of neutropenia defined by: 1) absolute neutrophil count (ANC) < 500 cells/mm^3 or has an ANC that is expected to decrease to < 500 cells/mm^3 within 48 hours of trial entry and fever defined as: 2) single oral temperature measurement of > 101 degree Fahrenheit (F) (38.3 degree Celsius [C]) or a temperature of > 100.4 degree F (38.0 degree C) sustained over a 1-hour period
- Requires hospitalization for IV empiric antibiotic therapy
- If female: not breastfeeding; agrees to not attempt to become pregnant during the study; is surgically sterile or at least 2-years postmenopausal, or if of childbearing potential, has negative screening serum pregnancy test (if serum pregnancy test results are not available at the time of enrollment, a negative urine pregnancy test is required within 24 hours.); if of childbearing potential (including being < 2 years postmenopausal), is willing to practice sexual abstinence or use an effective dual form of contraception with her partner (eg, 2 barrier methods, barrier method plus hormonal method) during treatment and for ≥ 28 days after the last dose of any study therapy (IV or oral)
Key exclusion criteria (17 listed)
- History of any hypersensitivity or allergic reaction to any cephalosporin antibiotic or tazobactam
- Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or blood product administration)
- Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with pneumonia) that justifies adding additional empiric antimicrobial therapy (eg, antifungals)
- Confirmed viral infection that justifies adding additional empiric antiviral therapy (eg, ganciclovir, foscarnet)
- Known acute viral hepatitis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CefepimeGiven IV | Drug | Group II (standard of care antibiotic treatment) |
| CeftolozaneAlso: CXA-101Given IV | Drug | Group I (ceftolozane-tazobactam) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Group I (ceftolozane-tazobactam), Group II (standard of care antibiotic treatment) |
| MeropenemAlso: Meropenem Trihydrate, Merrem I.V., SM-7338Given IV | Drug | Group II (standard of care antibiotic treatment) |
| Piperacillin-TazobactamAlso: PIPER/TAZO, Piperacillin/Tazobactam, ZosynGiven IV | Drug | Group II (standard of care antibiotic treatment) |
| TazobactamAlso: YTR-830HGiven IV | Drug | Group I (ceftolozane-tazobactam), Group II (standard of care antibiotic treatment) |
Primary outcome
Number of Participants With Favorable Clinical Response at End of Inpatient Intravenous Therapy (EOIV)
Time frame: Within 72 hours after administration of the last dose of inpatient IV study drug
Resolution of all acute signs and symptoms of the primary infection or improvement to such an extent that no additional antibacterial therapy is required (ie, except for protocol-allowed adjunctive therapies and/or oral or IV switch) and such that no more than 14 days of total antibacterial therapy is required.
23 secondary outcomes
Number of Participants With Favorable Clinical Response in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set at EOIV.
Time frame: Within 72 hours after administration of the last dose of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the Clinically Evaluable (CE) Analysis Set at EOIV.
Time frame: Within 72 hours after administration of the last dose of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the MITT Analysis Set at TOC
Time frame: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the MITT Analysis Set at Late Follow-Up (LFU)
Time frame: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the mMITT Analysis Set at Test of Cure (TOC)
Time frame: 21 to 28 days after the start of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the mMITT Analysis Set at Late Follow-Up (LFU)
Time frame: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the CE Analysis Set at TOC
Time frame: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the CE Analysis Set at LFU.
Time frame: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Favorable Clinical Response in the ME Analysis Set at EOIV.
Time frame: Within 72 hours after administration of the last dose of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the ME Analysis Set at TOC
Time frame: 21 to 28 days after the start of inpatient IV study drug.
Number of Participants With Favorable Clinical Response in the ME Analysis Set at LFU.
Time frame: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Favorable Microbiological Response in the mMITT Analysis Set at EOIV.
Time frame: Within 72 hours after administration of the last dose of inpatient IV study drug
Favorable Microbiological Response in the mMITT Analysis Set at TOC.
Time frame: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Favorable Microbiological Response in the mMITT Analysis Set at LFU.
Time frame: 35 to 42 days after the start of inpatient IV study drug.
Number of Participants With Favorable Microbiological Response in the ME Analysis Set at EOIV.
Time frame: Within 72 hours after administration of the last dose of inpatient IV study drug
Number of Participants With Favorable Microbiological Response in the ME Analysis Set at TOC.
Time frame: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Favorable Microbiological Response in the ME Analysis Set at LFU
Time frame: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Infection-related Mortality in the MITT Analysis Set at TOC
Time frame: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Infection-related Mortality in the MITT Analysis Set at LFU
Time frame: 35 to 42 days after the start of inpatient IV study drug
Number of Participants With Infection-related Mortality the mMITT Analysis Set at TOC
Time frame: 21 to 28 days after the start of inpatient IV study drug
Number of Participants With Infection-related Mortality in the mMITT Analysis Set at LFU.
Time frame: 35 to 42 days after the start of inpatient IV study drug
30 Day All-cause Mortality in the MITT Analysis Set
Time frame: 30 days after the last dose of inpatient IV study drug
30 Day All-cause Mortality in the mMITT Analysis Set
Time frame: 30 days after the last dose of inpatient IV study drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35663286Chaftari AM, Hachem R, Malek AE, Mulanovich VE, Szvalb AD, Jiang Y, Yuan Y, Ali S, Deeba R, Chaftari P, Raad I. A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients With Hematological Malignancies. Open Forum Infect Dis. 2022 Feb 14;9(6):ofac079. doi: 10.1093/ofid/ofac079. eCollection 2022 Jun.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Issam I Raad principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cefepime, Ceftolozane and Laboratory Biomarker Analysis in people with Other Infectious Diseases, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Favorable Clinical Response at End of Inpatient Intravenous Therapy (EOIV) (time frame: Within 72 hours after administration of the last dose of inpatient IV study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03485950, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2022.