scholarly journals Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial

2017 ◽  
Vol 66 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Stella Stergiopoulos ◽  
Sara B Calvert ◽  
Carrie A Brown ◽  
Josephine Awatin ◽  
Pamela Tenaerts ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bacterial Pneumonia ◽  
Phase 3 ◽  
Cost Drivers ◽  
Hospital Acquired

scholarly journals A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

2021 ◽  
Author(s):  
Richard G Wunderink ◽  
Antoine Roquilly ◽  
Martin Croce ◽  
Daniel Rodriguez Gonzalez ◽  
Satoshi Fujimi ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Double Blind Study ◽  
Phase 3 ◽  
Gram Positive ◽  
Double Blind ◽  
Intention To Treat ◽  
The Difference ◽  
Hospital Acquired ◽  
Noninferiority Margin

Abstract Background Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP. Methods In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population. Results Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, –1.8%; 95% confidence interval [CI]: –8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, –7.6%; 97.5% CI: –15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively. Conclusions Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated. Clinical Trials Registration NCT02019420.

scholarly journals Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: subset analysis of the ASPECT-NP randomized, controlled phase 3 trial

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Jean-François Timsit ◽  
Jennifer A. Huntington ◽  
Richard G. Wunderink ◽  
Nobuaki Shime ◽  
Marin H. Kollef ◽  
...  
Keyword(s):  
Bacterial Pneumonia ◽  
Controlled Trial ◽  
Multivariable Logistic Regression Analysis ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Intention To Treat ◽  
Randomized Controlled ◽  
Hospital Acquired ◽  
The Impact ◽  
Treat Population

Abstract Background Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. Methods ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. Results Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI − 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. Conclusions There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. Trial registration clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757.

scholarly journals Cost Drivers of Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase Three Clinical Trials

2015 ◽  
Vol 2 (suppl_1) ◽  
Author(s):  
Stella Stergiopoulos ◽  
Pamela Tenaerts ◽  
Kenneth Getz ◽  
Carrie Brown ◽  
Josephine Awatin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Bacterial Pneumonia ◽  
Cost Drivers ◽  
Hospital Acquired

scholarly journals Outcomes in Participants with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane/Tazobactam Treatment of Nosocomial Pneumonia (ASPECT-NP)

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Jennifer A. Huntington ◽  
Brian Yu ◽  
Linping Li ◽  
Erin Jensen ◽  
Christopher Bruno ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Bacterial Pneumonia ◽  
Small Sample ◽  
Phase 3 ◽  
Intention To Treat ◽  
Dosing Regimens ◽  
Secondary Endpoints ◽  
Small Sample Sizes ◽  
Hospital Acquired

ABSTRACT In the phase 3 ASPECT-NP trial (NCT02070757), ceftolozane/tazobactam (C/T) was noninferior to meropenem for treatment of Gram-negative ventilated hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (vHABP/VABP). Here, we report outcomes in participants from ASPECT-NP with renal impairment (RI). Participants were categorized by their baseline renal function as follows: normal renal function (NRF; creatinine clearance [CLCR], ≥80 ml/min), mild RI (CLCR, >50 to <80 ml/min), moderate RI (CLCR, ≥30 to ≤50 ml/min), and severe RI (CLCR, ≥15 to <30 ml/min). Dosing of both study drugs was adjusted based on renal function. The following C/T doses were administered every 8 h: NRF or mild RI, 3 g; moderate RI, 1.5 g; and severe RI, 0.75 g. The primary and key secondary endpoints were day 28 all-cause mortality (ACM) and clinical response at the test-of-cure visit in the intention-to-treat (ITT) population, respectively. In the ITT population, day 28 ACM rates for the C/T arm versus the meropenem arm were 17.6% versus 19.1% (NRF), 36.6% versus 28.6% (mild RI), 31.4% versus 38.5% (moderate RI), and 35.3% versus 61.9% (severe RI). Rates of clinical cure in the ITT population for the C/T arm versus the meropenem arm were 58.1% versus 58.5% (NRF), 54.9% versus 45.5% (mild RI), 37.1% versus 42.3% (moderate RI), and 41.2% versus 47.6% (severe RI). Small sample sizes in the RI groups resulted in large 95% confidence intervals (CIs), limiting conclusive interpretation of the analysis. Both drugs were well tolerated across all renal function groups. Overall, these results support the use of the study dosing regimens of C/T for treatment of vHABP/VABP in patients with RI. (This study has been registered at ClinicalTrials.gov under identifier NCT02070757.)

scholarly journals Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

2021 ◽  
Vol 9 (1) ◽  
pp. 232596712097305
Author(s):  
Hong-Chul Lim ◽  
Yong-Beom Park ◽  
Chul-Won Ha ◽  
Brian J. Cole ◽  
Beom-Koo Lee ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Cartilage Repair ◽  
Older Patients ◽  
Cartilage Defects ◽  
Full Thickness ◽  
Phase 3 ◽  
Randomized Controlled ◽  
Cartilage Restoration

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group ( P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group ( P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group ( P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up ( P < .05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

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