Trial Outcomes & Findings for Clinical Trials to Reduce the Risk of Antimicrobial Resistance (NCT NCT01570192)
NCT ID: NCT01570192
Last Updated: 2017-09-29
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
43 participants
Primary outcome timeframe
up to 28 days after enrollment
Results posted on
2017-09-29
Participant Flow
We had 8 clinical sites: recruitment into the study began September 2010 and ended April 10, 2015.
Enrolled participants were excluded from the trial before assignment to groups because participants had no qualifying organisms; this includes participants with no growth on screening BAL, those with \< 104 CFU/mL on BAL, and those with only Gram-positive bacteria cultured from the BAL.
Participant milestones
| Measure |
IV Meropenem; Parenteral Aminoglycoside
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
30
|
|
Overall Study
COMPLETED
|
6
|
17
|
|
Overall Study
NOT COMPLETED
|
7
|
13
|
Reasons for withdrawal
| Measure |
IV Meropenem; Parenteral Aminoglycoside
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
|---|---|---|
|
Overall Study
no qualifying organism
|
6
|
12
|
|
Overall Study
changed to palliative care
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Clinical Trials to Reduce the Risk of Antimicrobial Resistance
Baseline characteristics by cohort
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=13 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=30 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Age, Continuous
|
61.2 years
STANDARD_DEVIATION 18.3 • n=5 Participants
|
58.4 years
STANDARD_DEVIATION 12.6 • n=7 Participants
|
59.2 years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
18 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Region of Enrollment
France
|
2 participants
n=5 Participants
|
11 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Baseline acute physiology and chronic health evaluation II (APACHE II) score
|
22.6 units on a scale
STANDARD_DEVIATION 4.6 • n=5 Participants
|
21.0 units on a scale
STANDARD_DEVIATION 6.2 • n=7 Participants
|
21.5 units on a scale
STANDARD_DEVIATION 5.8 • n=5 Participants
|
PRIMARY outcome
Timeframe: up to 28 days after enrollmentPopulation: All patients in the ME population with BAL at baseline and at Day 5/EE and pathogens collected at baseline BAL and at Day 5/EE BAL.
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.
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=6 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Number of Participants With Suppression and Emergence of Resistance
suppression of emergence of resistance
|
—
|
5 participants
|
—
|
—
|
|
Number of Participants With Suppression and Emergence of Resistance
emergence of resistance
|
—
|
1 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: End of treatment - up to 28 days after enrollmentPopulation: The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=4 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=15 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
n=6 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
n=18 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Clinical Response
|
2 Participants
|
8 Participants
|
2 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: End of treatment - up to 28 days after enrollmentPopulation: The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=3 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=5 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
n=4 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
n=6 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Clinical Response in Subjects Who Received Prior Antibiotics
|
1 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: End of treatment - up to 28 days after enrollmentPopulation: The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=4 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=15 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
n=6 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
n=18 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Overall Microbiologic Response
|
2 Participants
|
6 Participants
|
2 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: End of treatment - up to 28 days after enrollmentPopulation: The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=4 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=15 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
n=6 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
n=18 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Pretreatment Pathogen Response
|
3 Participants
|
9 Participants
|
3 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Day 5/Early ExtubationPopulation: The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=1 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=1 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
n=1 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
n=2 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Suppression of the Emergence of Resistance in Other Gram-negative Pathogens
|
1 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 5/Early ExtubationPopulation: The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.
Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=4 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=15 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
n=4 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
n=17 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Occurrence of Repeat Negative Cultures
|
3 Participants
|
6 Participants
|
3 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: 14 daysPopulation: The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.
Percentage of patients who died by efficacy endpoint, treatment group and population (n/N)
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=4 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=15 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
n=6 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
n=18 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Mortality
|
1 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 28 daysPopulation: The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.
Percentage of patients who died by efficacy endpoint, treatment group and population (n/N)
Outcome measures
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=4 Participants
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=15 Participants
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
m-MITT Group - Meropenem Plus Aminoglycoside
n=6 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
m-MITT Group - Meropenem Only
n=18 Participants
Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.
|
|---|---|---|---|---|
|
Mortality
|
2 Participants
|
1 Participants
|
3 Participants
|
3 Participants
|
Adverse Events
IV Meropenem; Parenteral Aminoglycoside
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
I.V. Meropenem
Serious events: 11 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
IV Meropenem; Parenteral Aminoglycoside
n=13 participants at risk
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.
IV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization: tobramycin nebulization 600mg/day
|
I.V. Meropenem
n=30 participants at risk
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.
I.V. Meropenem: 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
Linezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
cutaneous eruption
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
reinforced duodenal ulcer
|
7.7%
1/13 • Number of events 1
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
pneomonia
|
7.7%
1/13 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
|
Cardiac disorders
cardiogenic shock
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
|
Cardiac disorders
cardiac arrest
|
7.7%
1/13 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
COPD with acute exacerbation
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pneumothorax
|
7.7%
1/13 • Number of events 1
|
0.00%
0/30
|
|
Cardiac disorders
AICD fired/NSTEMI
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
|
Cardiac disorders
PEA arrest
|
7.7%
1/13 • Number of events 1
|
0.00%
0/30
|
|
General disorders
multi-organ failure
|
0.00%
0/13
|
6.7%
2/30 • Number of events 2
|
|
General disorders
multi-organ failure due to distributive and cardiogenic shock
|
7.7%
1/13 • Number of events 1
|
0.00%
0/30
|
|
General disorders
stroke
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
|
General disorders
pulmonary embolism
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
|
General disorders
refractory shock
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
|
General disorders
septic shock
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
|
General disorders
cardiorespiratory arrest
|
0.00%
0/13
|
3.3%
1/30 • Number of events 1
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. George L. Drusano
University of Florida, Department of Medicine
Phone: 407-313-7060
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60