Pneumonia, BacterialPhase 2NCT02218359
Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative and / or Gram-positive Bacterial Colonization
A Phase 2 study testing Amikacin Fosfomycin Inhalation Solution in people with Pneumonia, Bacterial, run by Cardeas Pharma.
Trial summary
To demonstrate the safety and efficacy of adjunctive therapy with the Amikacin Fosfomycin Inhalation System (AFIS) versus aerosolized placebo in mechanically ventilated patients with Gram-negative and / or Gram-positive bacterial colonization. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pneumonia, Bacterial
- What is being tested?
- Amikacin Fosfomycin Inhalation Solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Oct 2014to Jan 2016
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and non-pregnant, non-lactating females, ≥ 18 years and ≤ 80 years of age
- Intubated and mechanically-ventilated
- Presence of Gram-negative and/or Gram-positive organism(s) by culture of respiratory secretions from a sample obtained within the previous 7 days
Who cannot join
- History of hypersensitivity to amikacin or fosfomycin.
- Diagnosis of pneumonia, defined as presence of a new or progressive infiltrate(s) on chest radiograph (within 7 days prior to screening), as determined by the treating physician
- Use of systemic antibiotics with efficacy against likely respiratory tract pathogens at the time of randomization
- Severe acute respiratory distress syndrome (defined as PaO2/FiO2 ≤ 100 mmHg and diffuse infiltrates on Chest X-ray)
- Refractory septic shock (severe sepsis plus unstable hypotension, in spite of adequate fluid resuscitation and vasopressors)
- Evidence of significant renal impairment (serum creatinine > 4.0 mg/dL within 24 hours prior to screening) . If serum creatinine is > 2.0 mg/dL, site must be capable of performing continuous renal replacement therapy, if clinically indicated. Patients with serum creatinine > 4.0 mg/dL and being treated with continuous renal replacement therapy (continuous venous-venous hemofiltration or continuous venous-venous hemodialysis) or chronic hemodialysis are eligible
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- Evidence of ototoxicity (history of hearing aid use prior to current hospitalization)
- Evidence of hepatotoxicity (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3X the upper limit of normal value within 24 hours prior to screening)
- Any of the following conditions that interfere with the assessment or interpretation of the diagnosis or response to therapy: chest trauma with loss of stability of the thoracic cage following a fracture of the sternum, ribs, or both; increased amounts of fluid in the lung cavities requiring chest tube drainage; lung cancer within the last 2 years; lung abscess(s); anatomical bronchial obstruction; suspected atypical pneumonia; chemical pneumonitis (e.g., inhalation injury); cystic fibrosis; congestive heart failure (leading to a PaO2/FiO2 ratio ≤ 100 mmHg and diffuse infiltrates on Chest X-ray)
- Immunocompromised patients, including those with neutropenia NOT due to the current infection (absolute neutrophil count < 500/mm³), leukemia, lymphoma, human immunodeficiency virus (HIV) infection with CD4 count < 200 cells/mm3, or splenectomy; those who are early post-transplantation, are on cytotoxic chemotherapy, or are on high-dose steroids (e.g., > 40 mg of prednisone or its equivalent [> 160 mg hydrocortisone, > 32 mg methylprednisolone, > 6 mg dexamethasone, > 200 mg cortisone] daily for > 2 weeks)
- Positive urine and/or serum beta-hCG pregnancy test (only in women of reproductive age)
- Participating in or has participated in other investigational interventional studies (drug or device) within the last 30 days (or 5 times the half-life of the previously administered investigational compound, whichever is longer) prior to study treatment
About this study
Official title: A Randomized Double-Blind, Placebo-Controlled, Crossover to Open Label, Phase 2 Study of Aerosolized Amikacin and Fosfomycin Delivered Via the Investigational eFlow® AFIS Inline System in Mechanically Ventilated Patients With Gram-negative and/or Gram-positive Bacterial Colonization
To demonstrate the safety and efficacy of adjunctive therapy with the Amikacin Fosfomycin Inhalation System (AFIS) versus aerosolized placebo in mechanically ventilated patients with Gram-negative and / or Gram-positive bacterial colonization.
Read the detailed description
The primary purpose of this study is to demonstrate the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS). AFIS consists of amikacin solution (AMS) and fosfomycin solution (FFS), delivered by aerosol to the lungs via the Investigational eFlow AFIS Inline System (AFIS Inline System) with tamper evident reservoir. Patients will be randomized to receive 5 days of treatment with either AFIS or placebo, followed by all patients receiving open label AFIS for five days. The primary efficacy endpoint is the change from baseline in tracheal aspirate Gram-negative and/or Gram-positive bacterial density at the end of the 5-day randomized course of study drug.
- Conditions
- Pneumonia, Bacterial
- Being tested
- Amikacin Fosfomycin Inhalation Solution, Aerosolized placebo
- Keywords
- Gram-negative pneumonia, Aerosol antibiotics, Mechanical ventilation, Amikacin, Fosfomycin, Pneumonia, Bacterial, Pneumonia, Bacterial Infections, Lung Diseases, Respiratory Tract Diseases, Respiratory Tract Infections, Anti-Bacterial Agents, Anti-Infective Agents, Therapeutic Uses, Pharmacologic Actions, MRSA
- Medical subject headings
- Pneumonia, Bacterial, Pneumonia, Bacterial Infections, Lung Diseases, Respiratory Tract Diseases, Respiratory Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amikacin Fosfomycin Inhalation SolutionDrug
Also called Amikacin Fosfomycin Inhalation System (AFIS), eFlow Inline System
300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the AFIS Inline System
Aerosolized placeboDrug
Also called eFlow Inline System
Placebo twice daily for Days 1 -5 to be administered by aerosol using the eFlow Inline System.
Amikacin Fosfomycin Inhalation SolutionDrug
Also called Amikacin Fosfomycin Inhalation System (AFIS), eFlow Inline System
Open-label crossover for all patients Days 6-10
| Study group | Role | What they receive |
|---|---|---|
| Amikacin Fosfomycin Inhalation Solution | Experimental | 300 mg of amikacin and 120 mg of fosfomycin to be administered by aerosol via the AFIS Inline System. Receives: Drug: Amikacin Fosfomycin Inhalation Solution |
| Aerosolized Placebo | Placebo comparator | Aerosolized placebo to be administered by aerosol using the AFIS Inline System. Receives: Drug: Aerosolized placebo; Drug: Amikacin Fosfomycin Inhalation Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density
Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density at the end of the 5-day randomized course of study drug
Measured: 5 day randomized course of study drug
Secondary outcomes (5)
Microbiological response rate in patients with multidrug resistant Gram-negative bacteria
Microbiological response rates at Day 5 in patients whose pre-study treatment tracheal aspirate culture was positive for multidrug resistant (MDR) Gram-negative bacteria
Measured: Day 5
Eradication of bacteria
Eradication of bacteria at Days 10, 21, and 28
Measured: Days 10, 21, and 28
Clinical worsening
Clinical worsening (defined as requiring institution of IV antibiotics) from Day 1 through Day 28
Measured: Day 1 - Day 28
Microbiological response rates
Microbiological response rates at Day 10 in all patients
Measured: Day 10
Microbiological response rates in patients with MRSA
Microbiological response rates at Day 5 in patients whose pre-study treatment tracheal aspirate culture was positive for methicillin resistant Staphylococcus aureus (MRSA)
Measured: Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2015 (estimated)
- Study completionJan 2016 (estimated)
Why it stopped: No Participants Enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pneumonia, BacterialStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cardeas Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bruce Montgomery, M.D., Study director, Cardeas Pharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02218359
- Sponsor's protocol ID
- CAP-01-103
- Status last verified
- Nov 2015
- First submitted
- 14 Aug 2014
- Last updated
- 18 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blind, Placebo-Controlled, Crossover to Open Label, Phase 2 Study of Aerosolized Amikacin and Fosfomycin Delivered Via the Investigational eFlow® AFIS Inline System in Mechanically Ventilated Patients With Gram-negative and/or Gram-positive Bacterial Colonization
- ClinicalTrials.gov ID
- NCT02218359
- Acronym / sponsor ID
- CAP-01-103
- Conditions
- Pneumonia, Bacterial
- Keywords
- Gram-negative pneumonia, Aerosol antibiotics, Mechanical ventilation, Amikacin, Fosfomycin, Pneumonia, Bacterial, Pneumonia, Bacterial Infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No Participants Enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cardeas PharmaIndustry (pharma, biotech, devices)
- Study start
- Oct 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Jan 2016 (estimated)
- First posted
- 18 Aug 2014 (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.
To demonstrate the safety and efficacy of adjunctive therapy with the Amikacin Fosfomycin Inhalation System (AFIS) versus aerosolized placebo in mechanically ventilated patients with Gram-negative and / or Gram-positive bacterial colonization.
Detailed description
The primary purpose of this study is to demonstrate the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS). AFIS consists of amikacin solution (AMS) and fosfomycin solution (FFS), delivered by aerosol to the lungs via the Investigational eFlow AFIS Inline System (AFIS Inline System) with tamper evident reservoir. Patients will be randomized to receive 5 days of treatment with either AFIS or placebo, followed by all patients receiving open label AFIS for five days. The primary efficacy endpoint is the change from baseline in tracheal aspirate Gram-negative and/or Gram-positive bacterial density at the end of the 5-day randomized course of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amikacin Fosfomycin Inhalation Solution | Experimental | Drug: Amikacin Fosfomycin Inhalation Solution300 mg of amikacin and 120 mg of fosfomycin to be administered by aerosol via the AFIS Inline System. |
| Aerosolized Placebo | Placebo comparator | Drug: Aerosolized placebo, Drug: Amikacin Fosfomycin Inhalation SolutionAerosolized placebo to be administered by aerosol using the AFIS Inline System. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males and non-pregnant, non-lactating females, ≥ 18 years and ≤ 80 years of age
- Intubated and mechanically-ventilated
- Presence of Gram-negative and/or Gram-positive organism(s) by culture of respiratory secretions from a sample obtained within the previous 7 days
Key exclusion criteria (12 listed)
- History of hypersensitivity to amikacin or fosfomycin.
- Diagnosis of pneumonia, defined as presence of a new or progressive infiltrate(s) on chest radiograph (within 7 days prior to screening), as determined by the treating physician
- Use of systemic antibiotics with efficacy against likely respiratory tract pathogens at the time of randomization
- Severe acute respiratory distress syndrome (defined as PaO2/FiO2 ≤ 100 mmHg and diffuse infiltrates on Chest X-ray)
- Refractory septic shock (severe sepsis plus unstable hypotension, in spite of adequate fluid resuscitation and vasopressors)
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 |
|---|---|---|
| Amikacin Fosfomycin Inhalation SolutionAlso: Amikacin Fosfomycin Inhalation System (AFIS), eFlow Inline System300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the AFIS Inline System | Drug | Amikacin Fosfomycin Inhalation Solution |
| Aerosolized placeboAlso: eFlow Inline SystemPlacebo twice daily for Days 1 -5 to be administered by aerosol using the eFlow Inline System. | Drug | Aerosolized Placebo |
| Amikacin Fosfomycin Inhalation SolutionAlso: Amikacin Fosfomycin Inhalation System (AFIS), eFlow Inline SystemOpen-label crossover for all patients Days 6-10 | Drug | Aerosolized Placebo, Amikacin Fosfomycin Inhalation Solution |
Primary outcome
Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density
Time frame: 5 day randomized course of study drug
Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density at the end of the 5-day randomized course of study drug
5 secondary outcomes
Microbiological response rate in patients with multidrug resistant Gram-negative bacteria
Time frame: Day 5
Eradication of bacteria
Time frame: Days 10, 21, and 28
Clinical worsening
Time frame: Day 1 - Day 28
Microbiological response rates
Time frame: Day 10
Microbiological response rates in patients with MRSA
Time frame: Day 5
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2015.
- MedlinePlus related topics: AntibioticsLink provided by the sponsor.
- MedlinePlus related topics: PneumoniaLink provided by the sponsor.
- Drug Information available for amikacinLink provided by the sponsor.
- Drug information available for fosfomycinLink provided by the sponsor.
- U.S. FDA ResourcesLink 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.
Bruce Montgomery, M.D. study director
Cardeas Pharma
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amikacin Fosfomycin Inhalation Solution in people with Pneumonia, Bacterial, run by Cardeas Pharma.
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 3 inclusion and 12 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: withdrawn, as of the sponsor's last update on 18 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 was withdrawn before enrolling participants, so there are no results.
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?
Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density (time frame: 5 day randomized course of study drug). 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 18 Nov 2015.