Cystic Fibrosis Pulmonary ExacerbationNCT01158937
Pharmacokinetic Study of Extended Infusion Meropenem in Adult Cystic Fibrosis Patients
A study testing Meropenem Infusion in people with Cystic Fibrosis Pulmonary Exacerbation, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Meropenem is an intravenous antibiotic commonly used to treat acute exacerbation of respiratory infections in cystic fibrosis. The research study aims to determine if a different method of infusing the drug over 3 hours or longer, instead of the traditional half-hour will improve target attainment of drug… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis Pulmonary Exacerbation
- What is being tested?
- Meropenem Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteCanada
- Study dates
- May 2010to Jan 2014
- 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
- ≥18 years old,
- currently experiencing new or exacerbation of active pulmonary infection as evidenced by increased coughing, sputum production, wheezing, white blood count and/or fever,
- requires meropenem for treatment,
- recent sputum culture positive for P. aeruginosa and/or B. cepacia at a prior visit,
- be able to provide written informed consent.
Who cannot join
- hypersensitivity and/or intolerance to meropenem,
- history of seizures,
- current use of valproic acid,
- significant psychiatric illness,
- contraindication to insertion of a venous catheter,
- worsening of clinical status requiring admission to intensive care unit (ICU),
- creatinine clearance ≤50 ml/min,
- significant cystic fibrosis-related liver dysfunction characterized by portal hypertension and cirrhosis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetic Study of Extended Infusion Meropenem in Adult Cystic Fibrosis Patient With Exacerbation of Pulmonary Infection
Meropenem is an intravenous antibiotic commonly used to treat acute exacerbation of respiratory infections in cystic fibrosis. The research study aims to determine if a different method of infusing the drug over 3 hours or longer, instead of the traditional half-hour will improve target attainment of drug concentrations and bactericidal activity. A secondary aim is to assess if the pharmacokinetics of meropenem is different during active infection compared to non-infective stage. Twelve patients admitted with acute respiratory infection and who requires meropenem will be enrolled into the study. Meropenem blood concentrations collected over 8 hours will be measured after half-hour and 3-hour infusions on different days. A pharmacokinetic modelling and Monte Carlo simulation program will use the data to assess and predict the optimal method of dosing. When patients return for a follow-up clinic visit, a single dose of meropenem will be administered and blood concentrations will be measured to determine the pharmacokinetics during non-infective stage.
Read the detailed description
Meropenem plays a crucial role in the treatment of pulmonary exacerbations in cystic fibrosis patients, because it has activity against both P. aeruginosa and B. cepacia, two of the most problematic pathogens that are encountered in this disease. These organisms cause chronic endobronchitis with frequent exacerbations which lead to significant morbidity and premature mortality. Treatment options for pulmonary exacerbations are limited due to the high rates of resistance with currently available antibiotics and lack of development of new effective antibiotics. Therefore optimization of the dosing of meropenem, by use of extended infusion strategy, is one method to allow us to maximize the efficacy of this drug. Meropenem is a beta-lactam type antibiotic with time-dependent bactericidal activity and hence it is suitable for extended infusion dosing. The key rationale for extended infusion of beta-lactam antibiotics is to allow for optimization of pharmacodynamic target attainment of time above the minimal inhibitory concentrations (T>MIC) to maximize bactericidal killing and optimize clinical outcomes. The use of this infusion strategy has been studied in non-cystic fibrosis patients treated primarily with piperacillin-tazobactam or meropenem for P. aeruginosa infections. The application of this strategy in cystic fibrosis patients has not been well studied, and there is no data for the treatment of B. cepacia infections. Also the pharmacokinetic characteristics of meropenem in adult cystic fibrosis patients with pulmonary exacerbation have not been previously studied. It is unclear whether or not the pharmacokinetic profile of meropenem in patients without exacerbation can be accurately extrapolated to those patients with exacerbation. The first phase of this study will, therefore, describe the pharmacokinetic profile of meropenem and the distribution of MICs for P. aeruginosa and B. cepacia in a population of adult cystic fibrosis patients with pulmonary exacerbation. The data will be used to determine an optimal extended infusion dosing strategy specifically for our patients with cystic fibrosis. The second phase of our study will provide additional data on the pharmacokinetics of meropenem in patients without active infection.
Significance of study:
This study will provide new information regarding the pharmacokinetics of meropenem in a population of cystic fibrosis patients with pulmonary exacerbation. This will allow us to apply Monte Carlo simulation to the data set with greater confidence as it directly reflects our own target population. Optimization of meropenem dosing based on pharmacodynamic profile and Monte Carlo simulation lays the groundwork for clinical efficacy studies in the future. Based on results from previous studies, optimization of meropenem dosing has the potential to produce better patient outcomes, reduce drug utilization and cost and reduce rates of resistance. These can be examined in future clinical studies.
- Conditions
- Cystic Fibrosis Pulmonary Exacerbation
- Being tested
- Meropenem Infusion
- Keywords
- meropenem, cystic fibrosis, extended infusion, pharmacokinetic
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Meropenem InfusionDrug
Also called Meropenem or Merrem(R)
Meropenem 2g infused intravenously over 30 mins (bolus infusion) Meropenem 2g infused intravenously over 3 hours (extended infusion)
| Study group | Role | What they receive |
|---|---|---|
| Extended Meropenem Infusion | Experimental | Meropenem Infusion over 3 hours Receives: Drug: Meropenem Infusion |
| Bolus Meropenem Infusion | Experimental | Meropenem infusion over 30 minutes Receives: Drug: Meropenem Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic profile of extended infusion meropenem in Cystic Fibrosis
Measured: Two x eight hour pharmacokinetic monitoring periods (carried over 2 days).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2010 (estimated)
- Study startMay 2010
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: Inadequate enrolment and lack of resources
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic Fibrosis Pulmonary ExacerbationStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe 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 N/A
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre, University of Toronto
- Responsible party
- Sponsor
- Investigators
- Daniel Cortes, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01158937
- Sponsor's protocol ID
- REB#08-316
- Status last verified
- May 2015
- First submitted
- 7 Jul 2010
- Last updated
- 21 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Study of Extended Infusion Meropenem in Adult Cystic Fibrosis Patient With Exacerbation of Pulmonary Infection
- ClinicalTrials.gov ID
- NCT01158937
- Acronym / sponsor ID
- REB#08-316
- Conditions
- Cystic Fibrosis Pulmonary Exacerbation
- Keywords
- meropenem, cystic fibrosis, extended infusion, pharmacokinetic
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate enrolment and lack of resources
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre, University of Toronto
- Study start
- May 2010
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 8 Jul 2010 (estimated)
- 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.
Meropenem is an intravenous antibiotic commonly used to treat acute exacerbation of respiratory infections in cystic fibrosis. The research study aims to determine if a different method of infusing the drug over 3 hours or longer, instead of the traditional half-hour will improve target attainment of drug concentrations and bactericidal activity. A secondary aim is to assess if the pharmacokinetics of meropenem is different during active infection compared to non-infective stage. Twelve patients admitted with acute respiratory infection and who requires meropenem will be enrolled into the study. Meropenem blood concentrations collected over 8 hours will be measured after half-hour and 3-hour infusions on different days. A pharmacokinetic modelling and Monte Carlo simulation program will use the data to assess and predict the optimal method of dosing. When patients return for a follow-up clinic visit, a single dose of meropenem will be administered and blood concentrations will be measured to determine the pharmacokinetics during non-infective stage.
Detailed description
Meropenem plays a crucial role in the treatment of pulmonary exacerbations in cystic fibrosis patients, because it has activity against both P. aeruginosa and B. cepacia, two of the most problematic pathogens that are encountered in this disease. These organisms cause chronic endobronchitis with frequent exacerbations which lead to significant morbidity and premature mortality. Treatment options for pulmonary exacerbations are limited due to the high rates of resistance with currently available antibiotics and lack of development of new effective antibiotics. Therefore optimization of the dosing of meropenem, by use of extended infusion strategy, is one method to allow us to maximize the efficacy of this drug. Meropenem is a beta-lactam type antibiotic with time-dependent bactericidal activity and hence it is suitable for extended infusion dosing. The key rationale for extended infusion of beta-lactam antibiotics is to allow for optimization of pharmacodynamic target attainment of time above the minimal inhibitory concentrations (T>MIC) to maximize bactericidal killing and optimize clinical outcomes. The use of this infusion strategy has been studied in non-cystic fibrosis patients treated primarily with piperacillin-tazobactam or meropenem for P. aeruginosa infections. The application of this strategy in cystic fibrosis patients has not been well studied, and there is no data for the treatment of B. cepacia infections. Also the pharmacokinetic characteristics of meropenem in adult cystic fibrosis patients with pulmonary exacerbation have not been previously studied. It is unclear whether or not the pharmacokinetic profile of meropenem in patients without exacerbation can be accurately extrapolated to those patients with exacerbation. The first phase of this study will, therefore, describe the pharmacokinetic profile of meropenem and the distribution of MICs for P. aeruginosa and B. cepacia in a population of adult cystic fibrosis patients with pulmonary exacerbation. The data will be used to determine an optimal extended infusion dosing strategy specifically for our patients with cystic fibrosis. The second phase of our study will provide additional data on the pharmacokinetics of meropenem in patients without active infection.
Significance of study:
This study will provide new information regarding the pharmacokinetics of meropenem in a population of cystic fibrosis patients with pulmonary exacerbation. This will allow us to apply Monte Carlo simulation to the data set with greater confidence as it directly reflects our own target population. Optimization of meropenem dosing based on pharmacodynamic profile and Monte Carlo simulation lays the groundwork for clinical efficacy studies in the future. Based on results from previous studies, optimization of meropenem dosing has the potential to produce better patient outcomes, reduce drug utilization and cost and reduce rates of resistance. These can be examined in future clinical studies.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Extended Meropenem Infusion | Experimental | Drug: Meropenem InfusionMeropenem Infusion over 3 hours |
| Bolus Meropenem Infusion | Experimental | Drug: Meropenem InfusionMeropenem infusion over 30 minutes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- ≥18 years old,
- currently experiencing new or exacerbation of active pulmonary infection as evidenced by increased coughing, sputum production, wheezing, white blood count and/or fever,
- requires meropenem for treatment,
- recent sputum culture positive for P. aeruginosa and/or B. cepacia at a prior visit,
- be able to provide written informed consent.
Key exclusion criteria (8 listed)
- hypersensitivity and/or intolerance to meropenem,
- history of seizures,
- current use of valproic acid,
- significant psychiatric illness,
- contraindication to insertion of a venous catheter,
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 |
|---|---|---|
| Meropenem InfusionAlso: Meropenem or Merrem(R)Meropenem 2g infused intravenously over 30 mins (bolus infusion) Meropenem 2g infused intravenously over 3 hours (extended infusion) | Drug | Bolus Meropenem Infusion, Extended Meropenem Infusion |
Primary outcome
Pharmacokinetic profile of extended infusion meropenem in Cystic Fibrosis
Time frame: Two x eight hour pharmacokinetic monitoring periods (carried over 2 days).
Results and safety
The study was stopped early (reason given: Inadequate enrolment and lack of resources). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2015.
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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.
Daniel Cortes principal investigator
Unity Health Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Meropenem Infusion in people with Cystic Fibrosis Pulmonary Exacerbation, run by Unity Health Toronto at 1 site in Canada.
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 5 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 21 May 2015. 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 Canada. 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: Inadequate enrolment and lack of resources). 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?
Pharmacokinetic profile of extended infusion meropenem in Cystic Fibrosis (time frame: Two x eight hour pharmacokinetic monitoring periods (carried over 2 days).). 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 21 May 2015.