SepsisNCT03019965
Efficacy of Betalactam Antibiotics in Prolonged Infusion Compared to Intermittent in Pediatric Patients With Sepsis
A study testing Intermittent Piperacillin/tazobactam, Continuous Piperacillin/tazobactam and Intermittent Imipenem in people with Sepsis, run by Coordinación de Investigación en Salud, Mexico at 2 sites in Mexico.
Trial summary
This study evaluates the efficacy and safety of the administration of betalactam antibiotics in prolonged infusion compared to intermittent infusion in children with sepsis. Half of participants will receive piperacillin/tazobactam, imipenem or meropenem in continuous or extended infusion, while the other half will… Read more about this study
- Who is it for?
- Ages 1 month to 17 years
- Conditions the study is for
- Sepsis
- What is being tested?
- Intermittent Piperacillin/tazobactam, Continuous Piperacillin/tazobactam and Intermittent Imipenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 426 participants
- Where
- 2 sitesMexico
- Study dates
- 1 Feb 2017to 30 Jan 2020
- Phase
- Interventional
- 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 1 month to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients diagnosed with sepsis, who have been evaluated by an infectious physician and are candidates to receive piperacillin/tazobactam, imipenem or meropenem as empiric treatment.
Who cannot join
- Patients with a history of allergy to one or more of the proposed antibiotics.
- Patients with chronic kidney disease or acute renal failure.
- Patients with acute liver failure of any cause.
- Patients in palliative or supportive care only.
Trial locations and contacts
2 sites in 1 country.
Mexico2 sites
Hospital Infantil de México Federico Gómez
Mexico City, Mexico City, 06720
Instituto Mexicano del Seguro Social
Mexico City, Mexico City, 06720
About this study
Official title: Efficacy and Safety of the Administration of Betalactam Antibiotics in Continuous or Extended Infusion Compared to Intermittent Infusion in Patients With Sepsis in Two Pediatric Third-level Care Hospitals
This study evaluates the efficacy and safety of the administration of betalactam antibiotics in prolonged infusion compared to intermittent infusion in children with sepsis. Half of participants will receive piperacillin/tazobactam, imipenem or meropenem in continuous or extended infusion, while the other half will receive piperacillin/tazobactam, imipenem or meropenem in intermittent infusion.
Read the detailed description
Sepsis is the leading cause of morbidity and mortality in hospitalised patients globally. Betalactams are time-dependent antibiotics, and so, the duration of time for which the free drug plasma concentration remains above the minimum inhibitory concentration (fT > MIC) is the pharmacokinetic/pharmacodynamic index associated with bacterial killing and clinical improvement. Numerous studies have demonstrated that continuous infusion (infusion in 24 hours) and extended infusion (through prolonging the infusion time to greater than 3 hours) allows the maintenance of concentrations above the MIC for a longer period of time within the dosing interval (30 minute or 1 hour), and so, capitalises on the pharmacodynamic properties of betalactams and maximises bacterial killing, therefore potentially improving clinical outcomes. In adult patients, the several studies suggest that prolonged infusion may offer clinical benefits and significant reduction in mortality without increasing the risk of toxicity, however, there is limited information about these dosing strategies in pediatric patients.
- Conditions
- Sepsis
- Being tested
- Intermittent Piperacillin/tazobactam, Continuous Piperacillin/tazobactam, Intermittent Imipenem, Extended Imipenem, Intermittent Meropenem
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent Piperacillin/tazobactamDrug
Also called Intermittent Infusion of Piperacillin/tazobactam, PiSA
Piperacillin/tazobactam administered in 30 minutes infusion.
Continuous Piperacillin/tazobactamDrug
Also called Continuous Infusion of Piperacillin/tazobactam, PiSA
Piperacillin/tazobactam administered in 24 hours infusion.
Intermittent ImipenemDrug
Also called Intermittent Infusion of Imipenem, PiSA
Imipenem administered in 60 minutes infusion.
Extended ImipenemDrug
Also called Extended Infusion of Imipenem, PiSA
Imipenem administered in 6 hours infusion.
Intermittent MeropenemDrug
Also called Intermittent Infusion of Meropenem, Kener, Merrem, AstraZeneca
Meropenem administered in 60 minutes infusion.
Extended MeropenemDrug
Also called Extended Infusion of Meropenem, Kener, Merrem, AstraZeneca
Meropenem administered in 8 hours infusion.
| Study group | Role | What they receive |
|---|---|---|
| Intermittent Piperacillin/tazobactam | Active comparator | Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours. Receives: Drug: Intermittent Piperacillin/tazobactam |
| Continuous Piperacillin/tazobactam | Experimental | Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature. Receives: Drug: Continuous Piperacillin/tazobactam |
| Intermittent Imipenem | Active comparator | Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours. Receives: Drug: Intermittent Imipenem |
| Extended Imipenem | Experimental | Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature. Receives: Drug: Extended Imipenem |
| Intermittent Meropenem | Active comparator | Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours. Receives: Drug: Intermittent Meropenem |
| Extended Meropenem | Experimental | Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature. Receives: Drug: Extended Meropenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinical Response
Resolution. Disappearance of all signs and symptoms related to the infection.
Failure. Insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).
Measured: Number of participants with clinical response at 14 days after antibiotic cessation, up to an average of 28 days or the day of your discharge if this occurred before 14 days after antibiotic cessation.
Secondary outcomes (1)
Number of Participants With Adverse Events
Any harmful, undesirable, potentially serious and life threatening effects occurring during or after administration of the antibiotics proposed in this study (piperacillin / tazobactam, imipenem or meropenem), was evaluated as: none or adverse event classified according to the intensity of the clinical manifestation (severity) as: mild, moderate or severe and for each antibiotic.
Measured: Number of participants with adverse events evaluated by an physician at the time of administration of antibiotics, up to an average to 24 hours after the study drug cessation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2017 (estimated)
- Study start1 Feb 2017
- Primary completion30 Dec 2019
- Study completion30 Jan 2020
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.
- Other trials for SepsisStudies 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
- 426 participants (actual)
Sponsor and investigators
- Lead sponsor
- Coordinación de Investigación en Salud, Mexico
- Sponsor type
- Other government
- Collaborators
- Instituto Mexicano del Seguro Social, Hospital Infantil de Mexico Federico Gomez, Hospital Regional de Alta Especialidad del Bajio
- Responsible party
- Principal investigator, Yazmín Del Carmen Fuentes Pacheco, Coordinación de Investigación en Salud, Mexico
- Investigators
- Yazmín del Carmen Fuentes, Principal investigator, Instituto Mexicano del Seguro Social
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03019965
- Sponsor's protocol ID
- 2016-785-099
- Status last verified
- Jul 2021
- First submitted
- 26 Dec 2016
- Last updated
- 5 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Identified individual participant data for all primary and secondary outcome measures will be made available within six months of study completion
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of the Administration of Betalactam Antibiotics in Continuous or Extended Infusion Compared to Intermittent Infusion in Patients With Sepsis in Two Pediatric Third-level Care Hospitals
- ClinicalTrials.gov ID
- NCT03019965
- Acronym / sponsor ID
- 2016-785-099
- Conditions
- Sepsis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 426 participants (actual)
- Lead sponsor
- Coordinación de Investigación en Salud, MexicoOther government
- Collaborators
- Instituto Mexicano del Seguro Social, Hospital Infantil de Mexico Federico Gomez, Hospital Regional de Alta Especialidad del Bajio
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 30 Dec 2019 (actual)
- Study completion
- 30 Jan 2020 (actual)
- First posted
- 13 Jan 2017 (estimated)
- Results
- Posted 5 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the efficacy and safety of the administration of betalactam antibiotics in prolonged infusion compared to intermittent infusion in children with sepsis. Half of participants will receive piperacillin/tazobactam, imipenem or meropenem in continuous or extended infusion, while the other half will receive piperacillin/tazobactam, imipenem or meropenem in intermittent infusion.
Detailed description
Sepsis is the leading cause of morbidity and mortality in hospitalised patients globally. Betalactams are time-dependent antibiotics, and so, the duration of time for which the free drug plasma concentration remains above the minimum inhibitory concentration (fT > MIC) is the pharmacokinetic/pharmacodynamic index associated with bacterial killing and clinical improvement. Numerous studies have demonstrated that continuous infusion (infusion in 24 hours) and extended infusion (through prolonging the infusion time to greater than 3 hours) allows the maintenance of concentrations above the MIC for a longer period of time within the dosing interval (30 minute or 1 hour), and so, capitalises on the pharmacodynamic properties of betalactams and maximises bacterial killing, therefore potentially improving clinical outcomes. In adult patients, the several studies suggest that prolonged infusion may offer clinical benefits and significant reduction in mortality without increasing the risk of toxicity, however, there is limited information about these dosing strategies in pediatric patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Intermittent Piperacillin/tazobactam | Active comparator | Drug: Intermittent Piperacillin/tazobactamPiperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours. |
| Continuous Piperacillin/tazobactam | Experimental | Drug: Continuous Piperacillin/tazobactamPiperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature. |
| Intermittent Imipenem | Active comparator | Drug: Intermittent ImipenemImipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours. |
| Extended Imipenem | Experimental | Drug: Extended ImipenemImipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature. |
| Intermittent Meropenem | Active comparator | Drug: Intermittent MeropenemMeropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours. |
| Extended Meropenem | Experimental | Drug: Extended MeropenemMeropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature. |
Who may qualify
- Ages
- 1 month to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Patients diagnosed with sepsis, who have been evaluated by an infectious physician and are candidates to receive piperacillin/tazobactam, imipenem or meropenem as empiric treatment.
Key exclusion criteria (4 listed)
- Patients with a history of allergy to one or more of the proposed antibiotics.
- Patients with chronic kidney disease or acute renal failure.
- Patients with acute liver failure of any cause.
- Patients in palliative or supportive care only.
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 |
|---|---|---|
| Intermittent Piperacillin/tazobactamAlso: Intermittent Infusion of Piperacillin/tazobactam, PiSAPiperacillin/tazobactam administered in 30 minutes infusion. | Drug | Intermittent Piperacillin/tazobactam |
| Continuous Piperacillin/tazobactamAlso: Continuous Infusion of Piperacillin/tazobactam, PiSAPiperacillin/tazobactam administered in 24 hours infusion. | Drug | Continuous Piperacillin/tazobactam |
| Intermittent ImipenemAlso: Intermittent Infusion of Imipenem, PiSAImipenem administered in 60 minutes infusion. | Drug | Intermittent Imipenem |
| Extended ImipenemAlso: Extended Infusion of Imipenem, PiSAImipenem administered in 6 hours infusion. | Drug | Extended Imipenem |
| Intermittent MeropenemAlso: Intermittent Infusion of Meropenem, Kener, Merrem, AstraZenecaMeropenem administered in 60 minutes infusion. | Drug | Intermittent Meropenem |
| Extended MeropenemAlso: Extended Infusion of Meropenem, Kener, Merrem, AstraZenecaMeropenem administered in 8 hours infusion. | Drug | Extended Meropenem |
Primary outcome
Number of Participants With Clinical Response
Time frame: Number of participants with clinical response at 14 days after antibiotic cessation, up to an average of 28 days or the day of your discharge if this occurred before 14 days after antibiotic cessation.
Resolution. Disappearance of all signs and symptoms related to the infection. Failure. Insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).
1 secondary outcome
Number of Participants With Adverse Events
Time frame: Number of participants with adverse events evaluated by an physician at the time of administration of antibiotics, up to an average to 24 hours after the study drug cessation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Identified individual participant data for all primary and secondary outcome measures will be made available within six months of study completion
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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.
Yazmín del Carmen Fuentes principal investigator
Instituto Mexicano del Seguro Social
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intermittent Piperacillin/tazobactam, Continuous Piperacillin/tazobactam and Intermittent Imipenem in people with Sepsis, run by Coordinación de Investigación en Salud, Mexico at 2 sites in Mexico.
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 1 inclusion and 4 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 5 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Mexico. 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?
Yes. Results are posted in the registry (first posted 5 Aug 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 Clinical Response (time frame: Number of participants with clinical response at 14 days after antibiotic cessation, up to an average of 28 days or the day of your discharge if this occurred before 14 days after antibiotic cessation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Aug 2021.