Carbapenem-Resistant Enterobacteriaceae InfectionOPTIMISENCT05210387
Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections
A study testing Duration of therapy in people with Carbapenem-Resistant Enterobacteriaceae Infection and Bloodstream Infection, run by Hospital Moinhos de Vento at 29 sites in Brazil.
Trial summary
Antimicrobial resistance is a major global problem, particularly in hospital-acquired infections (HAIs). Gram-negative bacilli (GNB), including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most common pathogens associated with multidrug resistance and HAIs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carbapenem-Resistant Enterobacteriaceae Infection, Bloodstream Infection, Severe Infection
- What is being tested?
- Duration of therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 29 sitesBrazil
- Study dates
- 27 Jan 2022to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Infection's diagnosis while in the ICU
- Severe infection in any site (defined as the presence of sepsis/septic shock or bloodstream infection or pneumonia) associated with a positive culture by MRD-GNB (Acinetobacter baumannii complex, Pseudomonas aeruginosa, and Enterobacterales bacteria, only susceptible to carbapenems and/or polymyxins)
- Hemodynamically stable and afebrile (axillary temperature less than 37.8ºC) for at least 48 hours on day 7 of adequate antibiotic therapy
- Consent of the team providing care to the patient regarding their inclusion in the research
Who cannot join
- Inclusion in other experimental studies involving antimicrobial therapy
- Infections that have as the primary site: endocarditis/endovascular infection, necrotizing fasciitis, osteomyelitis, abdominal abscess or other abdominal infections requiring surgical intervention (except infections that have been treated surgically, with curative character within the first 3 days of appropriate antimicrobial therapy), central nervous system Infections, empyema, prosthetic infection;
- Immunosuppression defined as: neutrophil cells <1000/mm³ in the current hospitalization, HIV/AIDS diagnosis with last CD4 count <200/mm³, solid organ transplantation in the last year and/or need for increased immunosuppression due to acute rejection in the last year, hematopoietic stem cell transplantation in the last year, and/or current therapy for chronic graft-versus-host disease
- Positive blood cultures for the same pathogen within 48 hours prior to randomization, when collected
- Uncontrolled concomitant infection with another GNB (regardless of susceptibility profile)
- Previous inclusion in this study
- Known pregnancy
- Patient in palliative care who has already decided not to restart antimicrobials, if necessary, or hemodynamic support measures.
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
Brazil29 sites
Hospital São Lucas Sergipe - Rede D´or São Luiz
Aracaju, Sergipe
Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, Minas Gerais, 30150-221
Hospital Tacchini
Bento Gonçalves, Rio Grande do Sul, 95700-068
Instituto Hospital de Base do Distrito Federal
Brasília, Federal District, 70330-150
Hospital Universitário de Brasília
Brasília, Federal District, 70840-901
Hospital Geral Caxias do Sul
Caxias do Sul, Rio Grande do Sul, 95070-561
Hospital Cleriston de Andrade
Feira de Santana, Estado de Bahia, 44089-340
Hospital OTO clinica
Fortaleza, Ceará
Hospital Dr. Léo Orsi Bernadres - HLOB
Itapetininga, São Paulo, 18.030-070
Hospital Universitário da Universidade Estadual de Londrina
Londrina, Paraná, 86038-350
Hospital Municipal de Maringá
Maringá, Paraná, 87053-270
Hospital Vila da Serra (Instituto Materno Infantil de Minas Gerais S/A)
Nova Lima, Minas Gerais, 34000-000
Hospital do Tricentenário
Olinda, Pernambuco, 53120-420
Irmandade da Santa Casa de Misericórdia de Passos
Passos, Minas Gerais, 37904-020
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital Ernesto Dornelles
Porto Alegre, Rio Grande do Sul, 90160-092
Hospital Nossa Senhora da Conceição
Porto Alegre, Rio Grande do Sul
Hospital São Lucas da PUC
Porto Alegre, Rio Grande do Sul
Hospital Naval Marcílio Dias
Rio de Janeiro
Instituto Estadual do Cérebro Paulo Niemeyer (Pró Saúde- Associação Beneficente de Assistência Social e Hospitalar)
Rio de Janeiro
Hospital Couto Maia
Salvador, Estado de Bahia
Hospital da Cidade
Salvador, Estado de Bahia
Hospital Santa Cruz
Santa Cruz do Sul, Rio Grande do Sul, 96810-072
Hospital Ana Nery
Santa Cruz do Sul, Rio Grande do Sul, 96835-090
Hospital Regional Baixo Amazonas
Santarém, Pará
Hospital Presidente Vargas
São Luís, Maranhão, 65040-450
Hospital A.C Camargo
São Paulo
Hospital Evangélico de Vila Velha
Vila Velha, Espírito Santo, 29118-060
Hospital São João Batista
Volta Redonda, Rio de Janeiro
About this study
Official title: Open-label, Randomized Clinical Trial to Assess the Non-inferiority of 7-day Antibiotic Therapy Compared to Conventional 14-day Treatment in Multidrug-resistant Gram-negative Bacilli Infections
Antimicrobial resistance is a major global problem, particularly in hospital-acquired infections (HAIs). Gram-negative bacilli (GNB), including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most common pathogens associated with multidrug resistance and HAIs. These bacteria are of special concern because few therapeutic options are available.
Traditionally, the duration of treatment for severe multidrug-resistant (MDR)-GNB infections is 14 days. Studies of severe infections by GNB, regardless of susceptibility profile, have shown that shorter antimicrobial treatments are not inferior to traditional durations of therapy and are associated with a lower incidence of adverse effects. However, there are currently no studies assessing whether shorter duration of antimicrobial treatment is effective for MDR-GNB.
This open-label, randomized clinical trial aims to assess the non-inferiority of 7-day antibiotic therapy compared to conventional 14-day treatment in severe infections by MDR-GNB.
- Conditions
- Carbapenem-Resistant Enterobacteriaceae Infection, Bloodstream Infection, Severe Infection, Pseudomonas Aeruginosa, Acinetobacter Infections, Gram-Negative Bacterial Infections
- Being tested
- Duration of therapy
- Medical subject headings
- Sepsis, Infections, Pseudomonas Infections, Acinetobacter Infections, Gram-Negative Bacterial Infections, Bacteremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Duration of therapyOther
In experimental group patients with severe infection caused by MDR-GNB and who present a clinical response on day 7 (±1) of adequate antimicrobial therapy, the therapy will be suspended.
The active control group will continue therapy until day 14 (±1).
| Study group | Role | What they receive |
|---|---|---|
| 7-day adequate antibiotic therapy | Experimental | Adequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility. Receives: Other: Duration of therapy |
| 14-day adequate antibiotic therapy | Active comparator | Adequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility. Receives: Other: Duration of therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical failure
Incidence of clinical failure. Clinical failure is a composite outcome defined by the presence of one of the following: Infection relapse (infection anywhere in the body by the same MDR-GNB) or Death
Measured: 28 days after randomization
Secondary outcomes (9)
Days alive and free from hospitalization
Number of days in which patients are alive and out of the hospital
Measured: 28 days after randomization
Days alive and free from any antibiotic therapy
Number of days in which patients are alive and free from any antibiotic therapy
Measured: 28 days after randomization
Occurrence of infections caused by other MRD-GNB or other bacteria
Incidence of infections caused by other MRD-GNB or other bacteria
Measured: 28 days after randomization
Length of intensive care unit stay
Number of days in which patients stayed at intensive care unit
Measured: 28 days after randomization
Acute kidney injury
Incidence of acute kidney injury, according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Measured: 28 days after randomization
Diarrhea for any cause
Incidence of any diarrhea. Diarrhea is defined as 3 or more episodes per day.
Measured: 28 days after randomization
Confirmed infection by Clostridioides difficile
Incidence of Clostridioides difficile infection
Measured: 28 days after randomization
Hemodynamic instability lasting more than 6 hours
Incidence of hemodynamic instability lasting more than 6 hours. Hemodynamic instability is defined as hypotension that requires the use of doses of dopamine above 15 mcg/kg/min, epinephrine above 0.1 mcg/kg/min, or norepinephrine above 0.1 mcg/kg/min
Measured: 14 days after randomization
Other adverse events related to antimicrobial therapy
Incidence of any other adverse event related to antimicrobial therapy
Measured: 28 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2022
- Study start27 Jan 2022
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Why it stopped: low recruitment rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Carbapenem-Resistant Enterobacteriaceae InfectionStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Moinhos de Vento
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexandre Prehn Zavascki, Principal investigator, Hospital Moinhos de Vento
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05210387
- Sponsor's protocol ID
- 47366621.1.1001.5330
- Acronym
- OPTIMISE
- Status last verified
- Sep 2023
- First submitted
- 31 Dec 2021
- Last updated
- 6 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Arns B, Kalil AC, Sorio GGL, Boschi E, Antonio ACP, Antonio JP, Birriel DC, Lanziotti DH, da Cunha Abbott F, Rocha GC, de Fatima Fernandes V, de Souza Dantas VC, da Silva Medeiros GF, de Franca Diniz Rocha V, Pereira FC, Gobatto ALN, Lima VP, Lacerda FH, de Maio Carrilho CMD, de Oliveira Cardozo KDN, Irineu VM, Kurtz P, Horvath JDC, Sesin GP, Agani CAJO, Dos Santos TM, Brochier LSB, da Rosa BS, Tomazini BM, Besen BAMP, Pereira AJ, Veiga VC, Nascimento GM, Zavascki AP; OPTIMISE Study Group. Seven versus 14 days of antimicrobial therapy for severe multidrug-resistant Gram-negative bacterial infections in intensive care unit patients (OPTIMISE): a randomised, open-label, non-inferiority clinical trial. Crit Care. 2024 Dec 18;28(1):412. doi: 10.1186/s13054-024-05178-6.
PubMed 39695798Arns B, Horvath JDC, Rech GS, Sesin GP, Agani CAJO, da Rosa BS, Dos Santos TM, Brochier LSB, Cavalcanti AB, Tomazini BM, Pereira AJ, Veiga VC, Nascimento GM, Kalil AC, Zavascki AP. A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol. Infect Dis Ther. 2024 Jan;13(1):237-250. doi: 10.1007/s40121-023-00897-9. Epub 2023 Dec 16.
PubMed 38102448
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Randomized Clinical Trial to Assess the Non-inferiority of 7-day Antibiotic Therapy Compared to Conventional 14-day Treatment in Multidrug-resistant Gram-negative Bacilli Infections
- ClinicalTrials.gov ID
- NCT05210387
- Acronym / sponsor ID
- OPTIMISE / 47366621.1.1001.5330
- Conditions
- Carbapenem-Resistant Enterobacteriaceae Infection, Bloodstream Infection, Severe Infection, Pseudomonas Aeruginosa, Acinetobacter Infections, Gram-Negative Bacterial Infections
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low recruitment rate
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Hospital Moinhos de VentoUniversity, hospital or other
- Study start
- 27 Jan 2022 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 27 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antimicrobial resistance is a major global problem, particularly in hospital-acquired infections (HAIs). Gram-negative bacilli (GNB), including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most common pathogens associated with multidrug resistance and HAIs. These bacteria are of special concern because few therapeutic options are available.
Traditionally, the duration of treatment for severe multidrug-resistant (MDR)-GNB infections is 14 days. Studies of severe infections by GNB, regardless of susceptibility profile, have shown that shorter antimicrobial treatments are not inferior to traditional durations of therapy and are associated with a lower incidence of adverse effects. However, there are currently no studies assessing whether shorter duration of antimicrobial treatment is effective for MDR-GNB.
This open-label, randomized clinical trial aims to assess the non-inferiority of 7-day antibiotic therapy compared to conventional 14-day treatment in severe infections by MDR-GNB.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 7-day adequate antibiotic therapy | Experimental | Other: Duration of therapyAdequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility. |
| 14-day adequate antibiotic therapy | Active comparator | Other: Duration of therapyAdequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Infection's diagnosis while in the ICU
- Severe infection in any site (defined as the presence of sepsis/septic shock or bloodstream infection or pneumonia) associated with a positive culture by MRD-GNB (Acinetobacter baumannii complex, Pseudomonas aeruginosa, and Enterobacterales bacteria, only susceptible to carbapenems and/or polymyxins)
- Hemodynamically stable and afebrile (axillary temperature less than 37.8ºC) for at least 48 hours on day 7 of adequate antibiotic therapy
- Consent of the team providing care to the patient regarding their inclusion in the research
Key exclusion criteria (8 listed)
- Inclusion in other experimental studies involving antimicrobial therapy
- Infections that have as the primary site: endocarditis/endovascular infection, necrotizing fasciitis, osteomyelitis, abdominal abscess or other abdominal infections requiring surgical intervention (except infections that have been treated surgically, with curative character within the first 3 days of appropriate antimicrobial therapy), central nervous system Infections, empyema, prosthetic infection;
- Immunosuppression defined as: neutrophil cells <1000/mm³ in the current hospitalization, HIV/AIDS diagnosis with last CD4 count <200/mm³, solid organ transplantation in the last year and/or need for increased immunosuppression due to acute rejection in the last year, hematopoietic stem cell transplantation in the last year, and/or current therapy for chronic graft-versus-host disease
- Positive blood cultures for the same pathogen within 48 hours prior to randomization, when collected
- Uncontrolled concomitant infection with another GNB (regardless of susceptibility profile)
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 |
|---|---|---|
| Duration of therapyIn experimental group patients with severe infection caused by MDR-GNB and who present a clinical response on day 7 (±1) of adequate antimicrobial therapy, the therapy will be suspended. The active control group will continue therapy until day 14 (±1). | Other | 14-day adequate antibiotic therapy, 7-day adequate antibiotic therapy |
Primary outcome
Clinical failure
Time frame: 28 days after randomization
Incidence of clinical failure. Clinical failure is a composite outcome defined by the presence of one of the following: Infection relapse (infection anywhere in the body by the same MDR-GNB) or Death
9 secondary outcomes
Days alive and free from hospitalization
Time frame: 28 days after randomization
Days alive and free from any antibiotic therapy
Time frame: 28 days after randomization
Occurrence of infections caused by other MRD-GNB or other bacteria
Time frame: 28 days after randomization
Length of intensive care unit stay
Time frame: 28 days after randomization
Acute kidney injury
Time frame: 28 days after randomization
Diarrhea for any cause
Time frame: 28 days after randomization
Confirmed infection by Clostridioides difficile
Time frame: 28 days after randomization
Hemodynamic instability lasting more than 6 hours
Time frame: 14 days after randomization
Other adverse events related to antimicrobial therapy
Time frame: 28 days after randomization
Results and safety
The study was stopped early (reason given: low recruitment rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Derived from this study: PubMed 39695798Arns B, Kalil AC, Sorio GGL, Boschi E, Antonio ACP, Antonio JP, Birriel DC, Lanziotti DH, da Cunha Abbott F, Rocha GC, de Fatima Fernandes V, de Souza Dantas VC, da Silva Medeiros GF, de Franca Diniz Rocha V, Pereira FC, Gobatto ALN, Lima VP, Lacerda FH, de Maio Carrilho CMD, de Oliveira Cardozo KDN, Irineu VM, Kurtz P, Horvath JDC, Sesin GP, Agani CAJO, Dos Santos TM, Brochier LSB, da Rosa BS, Tomazini BM, Besen BAMP, Pereira AJ, Veiga VC, Nascimento GM, Zavascki AP; OPTIMISE Study Group. Seven versus 14 days of antimicrobial therapy for severe multidrug-resistant Gram-negative bacterial infections in intensive care unit patients (OPTIMISE): a randomised, open-label, non-inferiority clinical trial. Crit Care. 2024 Dec 18;28(1):412. doi: 10.1186/s13054-024-05178-6.
- Derived from this study: PubMed 38102448Arns B, Horvath JDC, Rech GS, Sesin GP, Agani CAJO, da Rosa BS, Dos Santos TM, Brochier LSB, Cavalcanti AB, Tomazini BM, Pereira AJ, Veiga VC, Nascimento GM, Kalil AC, Zavascki AP. A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol. Infect Dis Ther. 2024 Jan;13(1):237-250. doi: 10.1007/s40121-023-00897-9. Epub 2023 Dec 16.
- Individual participant dataSharing planned: No
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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.
Alexandre Prehn Zavascki principal investigator
Hospital Moinhos de Vento
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Duration of therapy in people with Carbapenem-Resistant Enterobacteriaceae Infection and Bloodstream Infection, run by Hospital Moinhos de Vento at 29 sites in Brazil.
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 8 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: stopped early, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Brazil. 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.
Are results available for this study?
The study was stopped early (reason given: low recruitment rate). Results are not available in the source record.
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?
Clinical failure (time frame: 28 days after randomization). 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 NCT05210387, which also lists 2 linked publications.
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 6 Mar 2024.