Bacterial PneumoniaPhase 2NCT01570192
Clinical Trials to Reduce the Risk of Antimicrobial Resistance
A Phase 2 study testing IV meropenem, I.V. Meropenem and Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h in people with Bacterial Pneumonia, run by University of Florida at 11 sites in 4 countries.
Trial summary
The primary objective of this study is to demonstrate a low rate of emergence of antibiotic resistance in P. aeruginosa and Acinetobacter spp during the treatment of hospitalized patients with pneumonia requiring mechanical ventilation treated with PD optimized meropenem administered as a prolonged infusion in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacterial Pneumonia
- What is being tested?
- IV meropenem, I.V. Meropenem and Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 11 sitesin 4 countries
- Study dates
- Sep 2010to Apr 2015
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent by the subject/subject's LAR.
- Hospitalized males or females ≥ 18 yrs with respiratory failure requiring mechanical ventilation and clinical suspicion of HABP, HCAP or VABP.
- Onset or exacerbation of pneumonia at least 48 hours after admission to any patient health care facility or onset of pneumonia in a nursing home or rehabilitation facility with subsequent transfer to an acute care facility
- Women of childbearing potential if their pregnancy test is negative
- Subjects who have received previous antibacterial therapy within 14 days of pre-treatment bronchoscopy entry may be entered only if the subject has not responded clinically.). While less than 24 hours of pre-treatment antibiotics is preferential, recovery of >104 CFU/ml in the quantitative Bronchoscopic BAL will be seen as primary evidence that the prior therapy was not efficacious and enrollment will be allowed.)
- Patients should have clinical findings that support a diagnosis of HABP/VABP/HCAP:
Show all 9Show fewer
- Within 48 hours before starting empiric therapy a subject's chest radiograph should show the presence of a NEW or progressive infiltrate, cavitation, or effusion suggestive of pneumonia
- Within 36 hours before the start of empiric study therapy, a quantitative culture of Bronchoscopic BAL fluid must be obtained.
- Patients with VABP should have a Clinical Pulmonary Infection Score of >/= 5.
Who cannot join
- Subjects with pneumonia caused by pathogens resistant to meropenem (MIC greater than or equal to 16µg/ml) or a prior meropenem therapy failure.
- Subjects with contra-indications to ANY study medication, in particular with known or suspected allergy or hypersensitivity.
- Women who are pregnant or lactating.
- Subjects taking anticonvulsant medications for a known seizure disorder.Patients with a history of seizures, AND who are stabilized on anti-seizure medication, may be enrolled into the study at the discretion of the site investigator.
- Subjects with known or suspected community acquired bacterial pneumonia (CABP) or viral pneumonia; or Subjects with acute exacerbation of chronic bronchitis without evidence of pneumonia.
- Subjects with primary lung cancer or another malignancy metastatic to the lungs.
Show all 16Show fewer
- Subjects who were previously enrolled in this study.
- Subjects who have had an investigational drug or have used an investigational device within 30 days prior to entering the study.
- Subjects with another focus of infection requiring concurrent antibiotics that would interfere with evaluation of the response to study drug.
- Subjects with cystic fibrosis, AIDS with a CD4 lymphocyte count <200 cells/µl, neutropenia (absolute neutrophil count <500 cells/ml), known or suspected active tuberculosis.
- Subjects with little chance of survival for the duration of study therapy.
- Subjects with an APACHE II score >35.
- Subjects with underlying condition(s) which would make it difficult to interpret response to the study drugs.
- Subjects with hypotension or acidosis despite attempts at fluid resuscitation. Subjects requiring ongoing treatment with vasopressors will be eligible for the study if their hypotension is controlled and acidosis has resolved. Subjects with intractable septic shock are not eligible for enrollment.
- Subjects who have undergone bone marrow transplantation.
- Subjects with profound hypoxia as defined by a PaO2/FiO2 ratio <100.
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States8 sites
Emory University
Atlanta, Georgia, 30322-4250
Northwestern University
Chicago, Illinois, 60611
Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio, 44195
UFL Department of Medicine: Pulmonary, Critical Care and Sleep Medicine
Gainesville, Florida, 32610
Weill Cornell Medical Center of Cornell University
New York, New York, 10065
JMI Laboratories
North Liberty, Iowa, 52317
InClin, Inc.
San Mateo, California, 94403
Washington University in St. Louis School of Medicine
St Louis, Missouri, 63130
France1 site
Institut de Cardiologie, Groupe Hospitalier Pitie-Salpetriere
Paris, Cedex 13
About this study
Official title: Impact of Aggressive Empiric Antibiotic Therapy and Duration of Therapy on the Emergence of Antimicrobial Resistance During the Treatment of Hospitalized Subjects With Pneumonia Requiring Mechanical Ventilation
The primary objective of this study is to demonstrate a low rate of emergence of antibiotic resistance in P. aeruginosa and Acinetobacter spp during the treatment of hospitalized patients with pneumonia requiring mechanical ventilation treated with PD optimized meropenem administered as a prolonged infusion in combination with a parenteral aminoglycoside plus tobramycin by inhalation (Group 1) compared to therapy with meropenem alone (Group 2 - control arm).
Read the detailed description
The goal of this clinical study is to demonstrate that the application of pharmacodynamic dosing principles to the antibiotic treatment of hospitalized subjects with culture-documented pneumonia (including HABP, VABP and HCAP) requiring mechanical ventilation can inhibit the emergence of antibiotic-resistant organisms during treatment and therefore may improve the rate of a satisfactory clinical response. Antibiotic resistance is defined as an increase in meropenem or aminoglycoside MIC by two tube dilutions (fourfold) from baseline. In animal models of infection, the pharmacodynamic driver for bactericidal effect by β lactam antibiotics such as meropenem is the proportion of the dosing interval during which plasma drug levels are maintained above the MIC of the causative pathogen. The hypothesis of this study is that prolongation of time above MIC by increasing total meropenem dose and the duration of infusion will counter-select for the emergence of antimicrobial resistance during the treatment of hospitalized subjects with pneumonia (i.e. HABP, VABP and HCAP) caused by P.aeruginosa, Acinetobacter species (spp), or other pathogens with intermediate susceptibility to meropenem, and that the addition of parenteral aminoglycosides (amikacin, tobramycin or gentamicin) and nebulized aminoglycoside (tobramycin) given along optimal pharmacodynamic principles will further reduce the likelihood of resistance emergence, particularly among the non-fermenting Gram-negative bacilli, such as Pseudomonas aeruginosa and Acinetobacter spp. The observed incidence of resistance emergence to meropenem will be compared across therapeutic regimens.
- Conditions
- Bacterial Pneumonia
- Being tested
- IV meropenem, I.V. Meropenem, Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h, Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage., tobramycin nebulization
- Keywords
- gram negative pathogens, Pseudomonas aeruginosa, Acinetobacter, HCAP, VABP, HABP
- Medical subject headings
- Pneumonia, Bacterial, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV meropenemDrug
Also called Merrem I.V.
Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
I.V. MeropenemDrug
Also called Merrem I.V.
Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage
Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24hDrug
a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.Drug
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulizationDevice
tobramycin nebulization 600mg/day
| Study group | Role | What they receive |
|---|---|---|
| IV meropenem; parenteral aminoglycoside | Experimental | Subjects assigned to this group will receive:
* IV meropenem (2 g infused over 3 hrs q 8 hr);
* a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
* tobramycin nebulization
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat potential Gram-positive pathogens. Receives: Drug: IV meropenem; Drug: Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h; Drug: Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.; Device: tobramycin nebulization |
| I.V. Meropenem | Active comparator | Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat Gram-positive pathogens.
**NOTE: Empiric MRSA coverage is allowed in both arms. This therapy is advised for any subjects with known or suspected MRSA entering the study. Once microbiologic results are available, this coverage may be discontinued at the investigator's discretion. Receives: Drug: I.V. Meropenem; Drug: Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Suppression and Emergence of Resistance
The emergence of resistance is defined as a change of meropenem MIC or aminoglycoside MIC by two tube dilutions (fourfold) from baseline when assessed at the second BAL procedure on day 5/early extubation. Patients are evaluable for this endpoint IF they had baseline BAL and Day 5/early extubation and if they had positive cultures on baseline and Day/EE.
Measured: up to 28 days after enrollment
Secondary outcomes (8)
Clinical Response
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Measured: End of treatment - up to 28 days after enrollment
Clinical Response in Subjects Who Received Prior Antibiotics
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Measured: End of treatment - up to 28 days after enrollment
Overall Microbiologic Response
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Measured: End of treatment - up to 28 days after enrollment
Pretreatment Pathogen Response
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Measured: End of treatment - up to 28 days after enrollment
Suppression of the Emergence of Resistance in Other Gram-negative Pathogens
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Measured: Day 5/Early Extubation
Occurrence of Repeat Negative Cultures
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Measured: Day 5/Early Extubation
Mortality
Percentage of patients who died by efficacy endpoint, treatment group and population (n/N)
Measured: 14 days
Mortality
Percentage of patients who died by efficacy endpoint, treatment group and population (n/N)
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2012 (estimated)
- Study startSep 2010
- Primary completionApr 2015
- Study completionApr 2015
Why it stopped: NIAID terminated the study due to low subject enrollment
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.
- Publications (49)Papers the sponsor has linked to this study.
- Other trials for Bacterial PneumoniaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- George L Drusano, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01570192
- Sponsor's protocol ID
- 10-0060
- Status last verified
- Sep 2017
- First submitted
- 22 Mar 2012
- Last updated
- 29 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, American Thoracic Society, November 1995. Am J Respir Crit Care Med. 1996 May;153(5):1711-25. doi: 10.1164/ajrccm.153.5.8630626. No abstract available.
PubMed 8630626Bauernfeind A, Jungwirth R. In Vitro Activity of SM 7338 and Imipenem. 28th ICAAC, Los Angeles, October 1988. Abstract 599
Calandra GB, Hesney M, Brown KR. Imipenem/cilastatin therapy of serious infections: a U.S. multicenter noncomparative trial. Clin Ther. 1985;7(2):225-38.
PubMed 3886144Clarke AM, Zemcov SJV. SM 7338 (ICI 194,660), A New DHP-1 Stable Carbapenem; In Vitro Activity Against a Wide Range of Canadian Clinical Isolates. 28th ICAAC, Los Angeles, October 1988. Abstract 598.
Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998 Jan;26(1):1-10; quiz 11-2. doi: 10.1086/516284.
PubMed 9455502Craig WA. The pharmacology of meropenem, a new carbapenem antibiotic. Clin Infect Dis. 1997 Feb;24 Suppl 2:S266-75. doi: 10.1093/clinids/24.supplement_2.s266.
PubMed 9126702Dandekar PK, Maglio D, Sutherland CA, Nightingale CH, Nicolau DP. Pharmacokinetics of meropenem 0.5 and 2 g every 8 hours as a 3-hour infusion. Pharmacotherapy. 2003 Aug;23(8):988-91. doi: 10.1592/phco.23.8.988.32878.
PubMed 12921245Data on file. Drug Development Department, AstraZeneca Pharmaceuticals, Wilmington,DE 19897.
Drusano GL. Prevention of resistance: a goal for dose selection for antimicrobial agents. Clin Infect Dis. 2003 Jan 15;36(Suppl 1):S42-50. doi: 10.1086/344653.
PubMed 12516029Drusano GL, Liu W, Fregeau C, Kulawy R, Louie A. Differing effects of combination chemotherapy with meropenem and tobramycin on cell kill and suppression of resistance of wild-type Pseudomonas aeruginosa PAO1 and its isogenic MexAB efflux pump-overexpressed mutant. Antimicrob Agents Chemother. 2009 Jun;53(6):2266-73. doi: 10.1128/AAC.01680-08. Epub 2009 Mar 16.
PubMed 19289521Edwards JR, Wannop C. SM 7338, A New Carbapenem Antibacterial: In Vitro Activity Against Imipenem-Resistant Ps. aeruginosa. 27th ICAAC, New York October 1987, Abstract 754.
Edwards JR, Turner PJ, Withnell ES, et al. SM 7338, A New Carbapenem Antibacterial: In Vitro Activity Against Bacterial Strains of Clinical Origins. 27th ICAAC, New York, October 1987, Abstract 755.
Edwards JR, Turner PJ, Wannop C, Withnell ES, Grindey AJ, Nairn K. In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I. Antimicrob Agents Chemother. 1989 Feb;33(2):215-22. doi: 10.1128/AAC.33.2.215.
PubMed 2655530Fagon JY, Chastre J, Novara A, Medioni P, Gibert C. Characterization of intensive care unit patients using a model based on the presence or absence of organ dysfunctions and/or infection: the ODIN model. Intensive Care Med. 1993;19(3):137-44. doi: 10.1007/BF01720528.
PubMed 8315120Fink MP, Snydman DR, Niederman MS, Leeper KV Jr, Johnson RH, Heard SO, Wunderink RG, Caldwell JW, Schentag JJ, Siami GA, et al. Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group. Antimicrob Agents Chemother. 1994 Mar;38(3):547-57. doi: 10.1128/AAC.38.3.547.
PubMed 8203853
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Aggressive Empiric Antibiotic Therapy and Duration of Therapy on the Emergence of Antimicrobial Resistance During the Treatment of Hospitalized Subjects With Pneumonia Requiring Mechanical Ventilation
- ClinicalTrials.gov ID
- NCT01570192
- Acronym / sponsor ID
- 10-0060
- Conditions
- Bacterial Pneumonia
- Keywords
- gram negative pathogens, Pseudomonas aeruginosa, Acinetobacter, HCAP, VABP, HABP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: NIAID terminated the study due to low subject enrollment
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 4 Apr 2012 (estimated)
- Results
- Posted 20 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to demonstrate a low rate of emergence of antibiotic resistance in P. aeruginosa and Acinetobacter spp during the treatment of hospitalized patients with pneumonia requiring mechanical ventilation treated with PD optimized meropenem administered as a prolonged infusion in combination with a parenteral aminoglycoside plus tobramycin by inhalation (Group 1) compared to therapy with meropenem alone (Group 2 - control arm).
Detailed description
The goal of this clinical study is to demonstrate that the application of pharmacodynamic dosing principles to the antibiotic treatment of hospitalized subjects with culture-documented pneumonia (including HABP, VABP and HCAP) requiring mechanical ventilation can inhibit the emergence of antibiotic-resistant organisms during treatment and therefore may improve the rate of a satisfactory clinical response. Antibiotic resistance is defined as an increase in meropenem or aminoglycoside MIC by two tube dilutions (fourfold) from baseline. In animal models of infection, the pharmacodynamic driver for bactericidal effect by β lactam antibiotics such as meropenem is the proportion of the dosing interval during which plasma drug levels are maintained above the MIC of the causative pathogen. The hypothesis of this study is that prolongation of time above MIC by increasing total meropenem dose and the duration of infusion will counter-select for the emergence of antimicrobial resistance during the treatment of hospitalized subjects with pneumonia (i.e. HABP, VABP and HCAP) caused by P.aeruginosa, Acinetobacter species (spp), or other pathogens with intermediate susceptibility to meropenem, and that the addition of parenteral aminoglycosides (amikacin, tobramycin or gentamicin) and nebulized aminoglycoside (tobramycin) given along optimal pharmacodynamic principles will further reduce the likelihood of resistance emergence, particularly among the non-fermenting Gram-negative bacilli, such as Pseudomonas aeruginosa and Acinetobacter spp. The observed incidence of resistance emergence to meropenem will be compared across therapeutic regimens.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV meropenem; parenteral aminoglycoside | Experimental | Drug: IV meropenem, Drug: Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h, Drug: Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage., Device: tobramycin nebulizationSubjects assigned to this group will receive: * IV meropenem (2 g infused over 3 hrs q 8 hr); * a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h) * tobramycin nebulization Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat potential Gram-positive pathogens. |
| I.V. Meropenem | Active comparator | Drug: I.V. Meropenem, Drug: Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr). Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat Gram-positive pathogens. **NOTE: Empiric MRSA coverage is allowed in both arms. This therapy is advised for any subjects with known or suspected MRSA entering the study. Once microbiologic results are available, this coverage may be discontinued at the investigator's discretion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Written informed consent by the subject/subject's LAR.
- Hospitalized males or females ≥ 18 yrs with respiratory failure requiring mechanical ventilation and clinical suspicion of HABP, HCAP or VABP.
- Onset or exacerbation of pneumonia at least 48 hours after admission to any patient health care facility or onset of pneumonia in a nursing home or rehabilitation facility with subsequent transfer to an acute care facility
- Women of childbearing potential if their pregnancy test is negative
- Subjects who have received previous antibacterial therapy within 14 days of pre-treatment bronchoscopy entry may be entered only if the subject has not responded clinically.). While less than 24 hours of pre-treatment antibiotics is preferential, recovery of >104 CFU/ml in the quantitative Bronchoscopic BAL will be seen as primary evidence that the prior therapy was not efficacious and enrollment will be allowed.)
Key exclusion criteria (16 listed)
- Subjects with pneumonia caused by pathogens resistant to meropenem (MIC greater than or equal to 16µg/ml) or a prior meropenem therapy failure.
- Subjects with contra-indications to ANY study medication, in particular with known or suspected allergy or hypersensitivity.
- Women who are pregnant or lactating.
- Subjects taking anticonvulsant medications for a known seizure disorder.Patients with a history of seizures, AND who are stabilized on anti-seizure medication, may be enrolled into the study at the discretion of the site investigator.
- Subjects with known or suspected community acquired bacterial pneumonia (CABP) or viral pneumonia; or Subjects with acute exacerbation of chronic bronchitis without evidence of pneumonia.
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 |
|---|---|---|
| IV meropenemAlso: Merrem I.V.Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr). | Drug | IV meropenem; parenteral aminoglycoside |
| I.V. MeropenemAlso: Merrem I.V.Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr). Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage | Drug | I.V. Meropenem |
| Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24ha parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h) | Drug | IV meropenem; parenteral aminoglycoside |
| Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage. | Drug | I.V. Meropenem, IV meropenem; parenteral aminoglycoside |
| tobramycin nebulizationtobramycin nebulization 600mg/day | Device | IV meropenem; parenteral aminoglycoside |
Primary outcome
Number of Participants With Suppression and Emergence of Resistance
Time frame: up to 28 days after enrollment
The emergence of resistance is defined as a change of meropenem MIC or aminoglycoside MIC by two tube dilutions (fourfold) from baseline when assessed at the second BAL procedure on day 5/early extubation. Patients are evaluable for this endpoint IF they had baseline BAL and Day 5/early extubation and if they had positive cultures on baseline and Day/EE.
8 secondary outcomes
Clinical Response
Time frame: End of treatment - up to 28 days after enrollment
Clinical Response in Subjects Who Received Prior Antibiotics
Time frame: End of treatment - up to 28 days after enrollment
Overall Microbiologic Response
Time frame: End of treatment - up to 28 days after enrollment
Pretreatment Pathogen Response
Time frame: End of treatment - up to 28 days after enrollment
Suppression of the Emergence of Resistance in Other Gram-negative Pathogens
Time frame: Day 5/Early Extubation
Occurrence of Repeat Negative Cultures
Time frame: Day 5/Early Extubation
Mortality
Time frame: 14 days
Mortality
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8630626Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, American Thoracic Society, November 1995. Am J Respir Crit Care Med. 1996 May;153(5):1711-25. doi: 10.1164/ajrccm.153.5.8630626. No abstract available.
- BackgroundBauernfeind A, Jungwirth R. In Vitro Activity of SM 7338 and Imipenem. 28th ICAAC, Los Angeles, October 1988. Abstract 599
- Background: PubMed 3886144Calandra GB, Hesney M, Brown KR. Imipenem/cilastatin therapy of serious infections: a U.S. multicenter noncomparative trial. Clin Ther. 1985;7(2):225-38.
- BackgroundClarke AM, Zemcov SJV. SM 7338 (ICI 194,660), A New DHP-1 Stable Carbapenem; In Vitro Activity Against a Wide Range of Canadian Clinical Isolates. 28th ICAAC, Los Angeles, October 1988. Abstract 598.
- Background: PubMed 9455502Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998 Jan;26(1):1-10; quiz 11-2. doi: 10.1086/516284.
- Background: PubMed 9126702Craig WA. The pharmacology of meropenem, a new carbapenem antibiotic. Clin Infect Dis. 1997 Feb;24 Suppl 2:S266-75. doi: 10.1093/clinids/24.supplement_2.s266.
- Background: PubMed 12921245Dandekar PK, Maglio D, Sutherland CA, Nightingale CH, Nicolau DP. Pharmacokinetics of meropenem 0.5 and 2 g every 8 hours as a 3-hour infusion. Pharmacotherapy. 2003 Aug;23(8):988-91. doi: 10.1592/phco.23.8.988.32878.
- BackgroundData on file. Drug Development Department, AstraZeneca Pharmaceuticals, Wilmington,DE 19897.
- Background: PubMed 12516029Drusano GL. Prevention of resistance: a goal for dose selection for antimicrobial agents. Clin Infect Dis. 2003 Jan 15;36(Suppl 1):S42-50. doi: 10.1086/344653.
- Background: PubMed 19289521Drusano GL, Liu W, Fregeau C, Kulawy R, Louie A. Differing effects of combination chemotherapy with meropenem and tobramycin on cell kill and suppression of resistance of wild-type Pseudomonas aeruginosa PAO1 and its isogenic MexAB efflux pump-overexpressed mutant. Antimicrob Agents Chemother. 2009 Jun;53(6):2266-73. doi: 10.1128/AAC.01680-08. Epub 2009 Mar 16.
- BackgroundEdwards JR, Wannop C. SM 7338, A New Carbapenem Antibacterial: In Vitro Activity Against Imipenem-Resistant Ps. aeruginosa. 27th ICAAC, New York October 1987, Abstract 754.
- BackgroundEdwards JR, Turner PJ, Withnell ES, et al. SM 7338, A New Carbapenem Antibacterial: In Vitro Activity Against Bacterial Strains of Clinical Origins. 27th ICAAC, New York, October 1987, Abstract 755.
- 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.
George L Drusano, MD principal investigator
University of Florida
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IV meropenem, I.V. Meropenem and Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h in people with Bacterial Pneumonia, run by University of Florida at 11 sites in 4 countries.
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 9 inclusion and 16 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 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, France, Germany, 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?
Yes. Results are posted in the registry (first posted 20 Apr 2017). 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 Suppression and Emergence of Resistance (time frame: up to 28 days after enrollment). 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 NCT01570192, which also lists 49 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 29 Sep 2017.