Infectious EndocarditisPhase 2NCT03681431
Evaluation of an Antibiotic Regimen Pharmacokinetic Applicable to Enterococcus Faecalis Infective Endocarditis
A Phase 2 study testing Ceftriaxone 4g/ 24h and Ceftriaxone 2g/ 12h in people with Infectious Endocarditis, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 1 site in Spain.
Trial summary
The clinical trial is designed as a phase II, crossover clinical trial. It will be carried out in healthy volunteers, who will receive two different antibiotic regimen based on ceftriaxone. One of the regimens had shown clinical effectiveness in this scenario, but it is not suitable for OPAT programs. Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Infectious Endocarditis
- What is being tested?
- Ceftriaxone 4g/ 24h and Ceftriaxone 2g/ 12h
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSpain
- Study dates
- 23 Apr 2018to 23 May 2019
- Phase
- Phase 2
- 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 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female adults subjects.
- Weight between 40 and 105 kilograms, both included, and body mass index lower than 34 kilograms per square meter.
- The subject (or his/her "trusted representative") must have given his/her informed and signed consent approved by an Ethical Committee.
- The subject must have normal analytical values or abnormal without clinical significance of biochemical parameters, liver and kidney function panel test, hemogram and album level. A medical check will be run by workers of Infectious Diseases Department.
- The subject must have a normal physical examination or abnormal without clinical significance. A medical check will be run by workers of Infectious Diseases Department.
- The medication taken usually by the subjects will be check by the Pharmacy Department in order to find possible interactions with ceftriaxone.
Who cannot join
- Subjects with clinically significant abnormalities in laboratory test or physical exploration. A medical check will be run by workers of Infectious Diseases Department.
- Subjects undergoing an active infection find at the screening.
- Subjects with any clinical or surgery condition which contraindicate his/her inclusion, check by workers of Infectious Diseases Department.
- Subjects who has received treatment with cephalosporins 21 days before the trial starts or during the trial (apart from the protocol treatment).
- Subjects hypersensitive or allergic to cephalosporines or penicillins.
- Subjects undergoing chronic or acute cutaneous diseases which prevent the treatment administration.
- Subjects not giving his/her informed and signed consent approved by an Ethical Committee.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Clinical Trial to Evaluate an Antibiotic Regimen Pharmacokinetic Applicable to Outpatient Parenteral Antimicrobial Therapy in Enterococcus Faecalis Infective Endocarditis
The clinical trial is designed as a phase II, crossover clinical trial. It will be carried out in healthy volunteers, who will receive two different antibiotic regimen based on ceftriaxone. One of the regimens had shown clinical effectiveness in this scenario, but it is not suitable for OPAT programs. In the other hand, a new treatment schema useful in OPAT programs is proposed, but there is still a lack of pharmacokinetic data to support it. The plasma drug concentrations will be measured in both cases, comparing the minimal drug concentration observed and the pharmacokinetic profiles of the two regimens.
Read the detailed description
Infective endocarditis (IE) is an uncommon but virulent infection disease. One of the most frequent etiology for this infection is Enterococcus faecalis. IE treatment is difficult due to the characteristics of the infection itself, the bacterial species and the frequent comorbidities of the patients. A bactericidal antimicrobial treatment is mandatory for the resolution of this disease, but most antibiotics do not exhibit this effect against E. faecalis and have prompted the combination of an aminoglycoside and a cell-wall active agent (generally a β-lactam) as the standard treatment. This is a lengthy treatment (4-6 weeks) and its primary side effect is nephrotoxicity. Furthermore, aminoglycoside resistant strain's rates are increasing in USA and Europe, getting more complicated to establish an effective antibiotic regimen. Nowadays, patients with E. faecalis IE are old and often have significant underlying comorbidities with an increased risk of developing nephrotoxicity with aminoglycoside treatment. For this reason, and for the relevance of high-level aminoglycoside-resistant strains, some alternatives have been explored. A double β-lactam regimen is an option, despite the intrinsically resistance of E. faecalis to cephalosporins. The most studied combination is a regimen based on ampicillin plus ceftriaxone, which has shown a synergistic effect in vitro. This combination is as effective as ampicillin plus gentamycin, but with lower nephrotoxicity. Those patients need at least 4-6 weeks of treatment with a prolonged hospitalization. However, after 2 week of treatment some patients are clinically stabilized and could be benefit of an outpatient parenteral antibiotic therapy (OPAT) program. For that purpose, it is essential to design a treatment regimen, which ensures the effectiveness and safety of the treatment, based on stability and pharmacokinetic and pharmacodynamics (PK/PD) studies of the administered drugs. Furthermore, the logistic and schedule should be simple enough to enable the inclusion in an OPAT program. In order to design an antibiotic regimen suitable for OPAT programs and as effective as the standard therapies for E. faecalis IE, we decided to start clinical trial.
The clinical trial is designed as a phase II, crossover clinical trial. It will be carried out in healthy volunteers, who will receive two different antibiotic regimen based on ceftriaxone. One of the regimens had shown clinical effectiveness in this scenario, but it is not suitable for OPAT programs. In the other hand, a new treatment schema useful in OPAT programs is proposed, but there is still a lack of pharmacokinetic data to support it. The plasma drug concentrations will be measured in both cases, comparing the minimal drug concentration observed and the pharmacokinetic profiles of the two regimens.
- Conditions
- Infectious Endocarditis
- Being tested
- Ceftriaxone 4g/ 24h, Ceftriaxone 2g/ 12h
- Keywords
- Pharmacokinetic, Ceftriaxone, Enterococcus faecalis, Infectious Endocarditis
- Medical subject headings
- Endocarditis, Subacute Bacterial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftriaxone 4g/ 24hDrug
Each individual will be administrated 2 doses of 2 g of ceftriaxone separated for 12 hours. After a wash-out period (5-7 days) the same individuals will receive a single dose 4 g of ceftriaxone. In both cycles, plasma drug concentrations will be measure during 24 hours.
Ceftriaxone 2g/ 12hDrug
Each individual will be administrated 2 doses of 2 g of ceftriaxone separated for 12 hours. After a wash-out period (5-7 days) the same individuals will receive a single dose 4 g of ceftriaxone. In both cycles, plasma drug concentrations will be measure during 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Ceftriaxone 4g/ 24h | Experimental | Single intravenous dose of Ceftriaxone 4g/ 24h Receives: Drug: Ceftriaxone 4g/ 24h |
| Ceftriaxone 2g/ 12h | Active comparator | Two intravenous doses of Ceftriaxone 2g/ 12h Receives: Drug: Ceftriaxone 2g/ 12h |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum levels after 24 hours
To determinate whether 24 hours after the administration of 4 grams of ceftriaxone in a single short infusion, serums levels would be higher than 5 micrograms per millilitre
Measured: 24 hours
Secondary outcomes (6)
AUC 24 hours
To compare the 24 hours area under the curve (AUC) after the administration of 4 grams of ceftriaxone in a single short infusion and the administration of 2 grams of ceftriaxone in a two short infusions separated for 12 hours.
Measured: 24 hours
Plasma Clearance
To determinate ceftriaxone plasma clearance after the administration of 4 grams of ceftriaxone in a single short infusion.
Measured: 24 hours
Elimination Half-life
To determinate ceftriaxone elimination half-life after the administration of 4 grams of ceftriaxone in a single short infusion.
Measured: 24 hours
Volume of Distribution
To determinate ceftriaxone volume of distribution after the administration of 4 grams of ceftriaxone in a single short infusion.
Measured: 24 hours
Maximum Plasma Concentration
To determinate ceftriaxone maximum plasma concentration after the administration of 4 grams of ceftriaxone in a single short infusion.
Measured: 24 hours
Safety: Number, frequency and importance of adverse reactions.
To determinate the safety (number, frequency and importance of adverse reactions) of the administration of 4 grams of ceftriaxone in a single short infusion
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2018
- Study start23 Apr 2018
- Primary completion23 Apr 2019
- Study completion23 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infectious EndocarditisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- A phase II, single-centre, open, non-randomized, cross-over, clinical trial.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maria Victoria H Gil Navarro, Principal investigator, University Hospital Virgen del Rocio/ Institute of Biomedicine of Seville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03681431
- Sponsor's protocol ID
- ENDOKINETIC-CEF
- Status last verified
- Apr 2024
- First submitted
- 3 Aug 2018
- Last updated
- 3 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial to Evaluate an Antibiotic Regimen Pharmacokinetic Applicable to Outpatient Parenteral Antimicrobial Therapy in Enterococcus Faecalis Infective Endocarditis
- ClinicalTrials.gov ID
- NCT03681431
- Acronym / sponsor ID
- ENDOKINETIC-CEF
- Conditions
- Infectious Endocarditis
- Keywords
- Pharmacokinetic, Ceftriaxone, Enterococcus faecalis, Infectious Endocarditis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 23 Apr 2018 (actual)
- Primary completion
- 23 Apr 2019 (actual)
- Study completion
- 23 May 2019 (actual)
- First posted
- 24 Sep 2018 (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.
The clinical trial is designed as a phase II, crossover clinical trial. It will be carried out in healthy volunteers, who will receive two different antibiotic regimen based on ceftriaxone. One of the regimens had shown clinical effectiveness in this scenario, but it is not suitable for OPAT programs. In the other hand, a new treatment schema useful in OPAT programs is proposed, but there is still a lack of pharmacokinetic data to support it. The plasma drug concentrations will be measured in both cases, comparing the minimal drug concentration observed and the pharmacokinetic profiles of the two regimens.
Detailed description
Infective endocarditis (IE) is an uncommon but virulent infection disease. One of the most frequent etiology for this infection is Enterococcus faecalis. IE treatment is difficult due to the characteristics of the infection itself, the bacterial species and the frequent comorbidities of the patients. A bactericidal antimicrobial treatment is mandatory for the resolution of this disease, but most antibiotics do not exhibit this effect against E. faecalis and have prompted the combination of an aminoglycoside and a cell-wall active agent (generally a β-lactam) as the standard treatment. This is a lengthy treatment (4-6 weeks) and its primary side effect is nephrotoxicity. Furthermore, aminoglycoside resistant strain's rates are increasing in USA and Europe, getting more complicated to establish an effective antibiotic regimen. Nowadays, patients with E. faecalis IE are old and often have significant underlying comorbidities with an increased risk of developing nephrotoxicity with aminoglycoside treatment. For this reason, and for the relevance of high-level aminoglycoside-resistant strains, some alternatives have been explored. A double β-lactam regimen is an option, despite the intrinsically resistance of E. faecalis to cephalosporins. The most studied combination is a regimen based on ampicillin plus ceftriaxone, which has shown a synergistic effect in vitro. This combination is as effective as ampicillin plus gentamycin, but with lower nephrotoxicity. Those patients need at least 4-6 weeks of treatment with a prolonged hospitalization. However, after 2 week of treatment some patients are clinically stabilized and could be benefit of an outpatient parenteral antibiotic therapy (OPAT) program. For that purpose, it is essential to design a treatment regimen, which ensures the effectiveness and safety of the treatment, based on stability and pharmacokinetic and pharmacodynamics (PK/PD) studies of the administered drugs. Furthermore, the logistic and schedule should be simple enough to enable the inclusion in an OPAT program. In order to design an antibiotic regimen suitable for OPAT programs and as effective as the standard therapies for E. faecalis IE, we decided to start clinical trial.
The clinical trial is designed as a phase II, crossover clinical trial. It will be carried out in healthy volunteers, who will receive two different antibiotic regimen based on ceftriaxone. One of the regimens had shown clinical effectiveness in this scenario, but it is not suitable for OPAT programs. In the other hand, a new treatment schema useful in OPAT programs is proposed, but there is still a lack of pharmacokinetic data to support it. The plasma drug concentrations will be measured in both cases, comparing the minimal drug concentration observed and the pharmacokinetic profiles of the two regimens.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A phase II, single-centre, open, non-randomized, cross-over, clinical trial.
| Arm | Type | Receives |
|---|---|---|
| Ceftriaxone 4g/ 24h | Experimental | Drug: Ceftriaxone 4g/ 24hSingle intravenous dose of Ceftriaxone 4g/ 24h |
| Ceftriaxone 2g/ 12h | Active comparator | Drug: Ceftriaxone 2g/ 12hTwo intravenous doses of Ceftriaxone 2g/ 12h |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male and female adults subjects.
- Weight between 40 and 105 kilograms, both included, and body mass index lower than 34 kilograms per square meter.
- The subject (or his/her "trusted representative") must have given his/her informed and signed consent approved by an Ethical Committee.
- The subject must have normal analytical values or abnormal without clinical significance of biochemical parameters, liver and kidney function panel test, hemogram and album level. A medical check will be run by workers of Infectious Diseases Department.
- The subject must have a normal physical examination or abnormal without clinical significance. A medical check will be run by workers of Infectious Diseases Department.
Key exclusion criteria (7 listed)
- Subjects with clinically significant abnormalities in laboratory test or physical exploration. A medical check will be run by workers of Infectious Diseases Department.
- Subjects undergoing an active infection find at the screening.
- Subjects with any clinical or surgery condition which contraindicate his/her inclusion, check by workers of Infectious Diseases Department.
- Subjects who has received treatment with cephalosporins 21 days before the trial starts or during the trial (apart from the protocol treatment).
- Subjects hypersensitive or allergic to cephalosporines or penicillins.
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 |
|---|---|---|
| Ceftriaxone 4g/ 24hEach individual will be administrated 2 doses of 2 g of ceftriaxone separated for 12 hours. After a wash-out period (5-7 days) the same individuals will receive a single dose 4 g of ceftriaxone. In both cycles, plasma drug concentrations will be measure during 24 hours. | Drug | Ceftriaxone 4g/ 24h |
| Ceftriaxone 2g/ 12hEach individual will be administrated 2 doses of 2 g of ceftriaxone separated for 12 hours. After a wash-out period (5-7 days) the same individuals will receive a single dose 4 g of ceftriaxone. In both cycles, plasma drug concentrations will be measure during 24 hours. | Drug | Ceftriaxone 2g/ 12h |
Primary outcome
Serum levels after 24 hours
Time frame: 24 hours
To determinate whether 24 hours after the administration of 4 grams of ceftriaxone in a single short infusion, serums levels would be higher than 5 micrograms per millilitre
6 secondary outcomes
AUC 24 hours
Time frame: 24 hours
Plasma Clearance
Time frame: 24 hours
Elimination Half-life
Time frame: 24 hours
Volume of Distribution
Time frame: 24 hours
Maximum Plasma Concentration
Time frame: 24 hours
Safety: Number, frequency and importance of adverse reactions.
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
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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.
Maria Victoria H Gil Navarro principal investigator
University Hospital Virgen del Rocio/ Institute of Biomedicine of Seville
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 Ceftriaxone 4g/ 24h and Ceftriaxone 2g/ 12h in people with Infectious Endocarditis, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 1 site in Spain.
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 6 inclusion and 7 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 3 Apr 2024. 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 Spain. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Serum levels after 24 hours (time frame: 24 hours). 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 3 Apr 2024.