Phase 3
Completed N=69
A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE)
Bloodstream Infections (BSI) Due to CRE · Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE · Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE · Complicated Urinary Tract Infection (cUTI) Due to CRE
Source: ClinicalTrials.gov NCT01970371 ↗
Enrolled (actual)
69
Serious AEs
66.7%
Results posted
Oct 2018
Primary outcomePrimary: Percentage of Patients With All Cause Mortality (ACM) at Day 28 or Significant Disease-Related Complication (SDRC) in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1 — 23.5; 50 percentage of patients
◆ Published Evidence
Established
22citations · ~3 / year
Evaluation of Plazomicin, Tigecycline, and Meropenem Pharmacodynamic Exposure against Carbapenem-Resistant Enterobacteriaceae in Patients with Bloodstream Infection or Hospital-Acquired/Ventilator-Associated Pneumonia from the CARE Study (ACHN-490-007).
Summary
This was a Phase 3 study containing a randomized open-label superiority cohort (Cohort 1) comparing the efficacy and safety of plazomicin with colistin when combined with a second antibiotic (either meropenem or tigecycline) in the treatment of patients with bloodstream infection (BSI), hospital acquired bacterial pneumonia (HABP), or ventilator-associated bacterial pneumonia (VABP) due to CRE. An additional cohort of patients with BSI, HABP, VABP, complicated urinary tract infection (cUTI), or acute pyelonephritis (AP) due to CRE, not eligible for inclusion in the other cohort, were enrolled into a single arm (Cohort 2) and treated with plazomicin-based therapy. Therapeutic drug management (TDM) was used to help ensure that plazomicin exposures lie within an acceptable range of the target mean steady-state area under the curve (AUC).
Linked Publications
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Evaluation of Plazomicin, Tigecycline, and Meropenem Pharmacodynamic Exposure against Carbapenem-Resistant Enterobacteriaceae in Patients with Bloodstream Infection or Hospital-Acquired/Ventilator-Associated Pneumonia from the CARE Study (ACHN-490-007).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Patients With All Cause Mortality (ACM) at Day 28 or Significant Disease-Related Complication (SDRC) in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1 |
23.5; 50 | — |
| SECONDARY Percentage of Patients With ACM at Day 28 in the mMITT Population in Cohort 1 |
11.8; 40 | — |
| SECONDARY Percentage of Patients With Adjudicated Clinical Cure at the Test of Cure (TOC) Visit in the mMITT Population in Cohort 1 |
64.7; 45; 35.3; 55; 35.3; 35 | — |
| SECONDARY Time to Death Through Day 28 in the mMITT Population in Cohort 1 |
11.8; 40.0; 88.2; 60.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Patients With ACM at Day 14 in the mMITT Population in Cohort 1 |
5.9; 20 | — |
| SECONDARY Percentage of Patients With Dose Adjustment Due to Therapeutic Drug Management (TDM) |
77.8; 86.7 | — |
| SECONDARY Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) |
88.9; 100; 86.7 | — |
| SECONDARY Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h) |
235 | — |
| SECONDARY Plasma Pharmacokinetics (PK): Maximum Observed Plasma Drug Concentration (Cmax) |
37.1 | — |
| SECONDARY Plasma Pharmacokinetics (PK): Minimum Observed Plasma Drug Concentration (Cmin) |
2.1 | — |
Eligibility Criteria
Key Inclusion Criteria
- Cohort 1: APACHE II score between 15 and 30, inclusive; Cohort 2: BSI, HABP, VABP patients with an APACHE II score ≤30 (cUTI and AP patients do not need to have their APACHE II score calculated)
- Positive culture that was collected ≤96 hours prior to randomization indicating a CRE infection, or a high likelihood of a CRE infection
- Diagnosis of BSI as defined by at least one of the following: fever, hypothermia, new onset arterial hypotension, elevated total peripheral white blood cell (WBC) count, increased immature neutrophils (band forms), or leukopenia
- Or, diagnosis of HABP defined as clinical signs and symptoms consistent with pneumonia acquired after at least 48 hours of continuous stay in an inpatient acute or chronic-care facility, or acquired within 7 days after being discharged from a hospitalization of ≥3 days duration
- Or, diagnosis of VABP defined by clinical signs and symptoms consistent with pneumonia acquired after at least 48 hours of continuous mechanical ventilation
- Or, diagnosis of cUTI or AP defined by clinical signs and symptoms consistent with cUTI or AP assessed within 24 hours prior to enrollment
Key Exclusion Criteria
- Cohorts 1 and 2 BSI, HABP, and VABP patients: receipt of more than 72 hours of potentially effective antibacterial therapy; Cohort 2: cUTI and AP patients: receipt of any potentially effective antibacterial therapy in the 48 hours prior to enrollment
- Cohort 1 only: knowledge that index CRE infection is resistant to colistin prior to randomization
- Objective clinical evidence for any of the following clinical syndromes that necessitates study therapy for greater than 14 days: endovascular infection including endocarditis, osteomyelitis, prosthetic joint infection, meningitis and/or other central nervous system infections
- Objective clinical evidence of infectious involvement of intravascular material potentially due to the study qualifying pathogen and not intended to be removed within 4 calendar days of the initial positive culture
- HABP or VABP patients only: pulmonary disease that precludes evaluation of therapeutic response including known bronchial obstruction or a history of post-obstructive pneumonia, tracheobronchitis, primary lung cancer or malignancies metastatic to the lung, bronchiectasis, known or suspected active tuberculosis
- cUTI or AP patients only: renal abscess, chronic bacterial prostatitis, orchitis or epididymitis, polycystic kidney disease, one functional kidney, vesicoureteral reflux, renal transplant, cystectomy or ileal loop surgery, fungal UTI or complete, permanent obstruction of the urinary tract
- Patients in acute renal failure at the time of randomization
- Patients receiving intermittent hemodialysis (IHD) at the time of screening
- Pregnant or breastfeeding female patient
Data sourced from ClinicalTrials.gov (NCT01970371) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.