This site is intended for U.S. Healthcare Professionals only.

cIAI Trial—RECLAIM

cIAI Phase 3 clinical trial vs meropenem

STUDY DESIGN1

Type of Trial

Phase 3, multinational, double-blind, noninferiority trial

Study Population

1058 adults hospitalized with cIAI, which included appendicitis, cholecystitis, diverticulitis, gastric/duodenal perforation, perforation of the intestine, and other causes of intra-abdominal abscesses and peritonitis.

The microbiologically modified intent-to-treat (mMITT) population, which included all patients who had at least one baseline intra-abdominal pathogen regardless of the susceptibility to study drug, consisted of 823 patients; the median age was 51 years and 62.8% were male.

Comparative Agents

AVYCAZ® 2.5 g (2 g ceftazidime and 0.5 g avibactam) IV every 8 hours plus metronidazole 0.5 g IV every 8 hours

Meropenem 1 g IV every 8 hours

Treatment Duration

5 to 14 days

PRIMARY ENDPOINTS

Clinical cure—defined as complete resolution or significant improvement in signs and symptoms of the index infection—at the test-of-cure (TOC) visit in the mMITT population, which occurred 28 to 35 days after randomization.

IV, intravenous.

Clinical efficacy in cIAI demonstrated in a Phase 3 trial vs meropenem1

  • AVYCAZ plus metronidazole was noninferior to meropenem with regard to the clinical cure rate at the TOC visit in the mMITT population1

CLINICAL CURE RATES AT TOC (mMITT and ME*)1

chart depicting clinical cure rates at TOC

*The ME population included all protocol-adherent mMITT patients.1

TOC, test of cure.

mMITT, microbiologically modified intent-to-treat.

ME, microbiologically evaluable.

CI, confidence interval.

Subset populations

Clinical efficacy in cIAI caused by ceftazidime-NS Gram-negative pathogens1

  • At baseline, 111 patients in the mMITT population had Gram-negative isolates that were not susceptible to ceftazidime, including 61 patients with E. coli and 26 patients with K. pneumoniae1

CLINICAL CURE RATES AT TOC (mMITT): OVERALL ANALYSIS POPULATION AND CEFTAZIDIME-NS SUBSET POPULATION1

chart showing Clinical cure rates at TOC overall analysis subset populations

NS, nonsusceptible.

mMITT, microbiologically modified intent-to-treat.

TOC, test of cure.

Clinical efficacy in cIAI involving ESBLs and AmpC1

  • In a subset of Gram-negative pathogens from the Phase 3 cIAI trial, genotypic testing identified certain ESBL groups and AmpC in 12.8% (105/823) of patients in the mMITT population, all of which were expected to be inhibited by avibactam1:

TEM-1

SHV-12

CTX-M-15

OXA-48

AmpC

Clinical cure
rates in this
subset were
similar to the
overall results1

ESBLs, extended-spectrum β-lactamases.

mMITT, microbiologically modified intent-to-treat.

Clinical data by pathogen

CLINICAL CURE RATES BY BASELINE PATHOGEN AT TOC (mMITT)1

Graphic showing clinical cure rates by baseline pathogen

TOC, test of cure.

INDICATIONS AND USAGE

Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP)

AVYCAZ® (ceftazidime and avibactam) is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by the following susceptible Gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae in patients 18 years or older.

Complicated Intra-Abdominal Infections (cIAI)

AVYCAZ, in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa in patients 18 years or older.

Complicated Urinary Tract Infections (cUTI), including Pyelonephritis

AVYCAZ is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa in patients 18 years or older.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVYCAZ and other antibacterial drugs, AVYCAZ should be used to treat only indicated infections that are proven or strongly suspected to be caused by susceptible bacteria.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

AVYCAZ is contraindicated in patients with known serious hypersensitivity to the components of AVYCAZ (ceftazidime and avibactam), avibactam-containing products, or other members of the cephalosporin class.

WARNINGS AND PRECAUTIONS

  • In a Phase 3 cIAI trial, clinical cure rates were lower in a subgroup of patients with baseline creatinine clearance (CrCl) of 30 to less than or equal to 50 mL/min compared to those with CrCl greater than 50 mL/min. The reduction in clinical cure rates was more marked in patients treated with AVYCAZ plus metronidazole compared to meropenem-treated patients. Within this subgroup, patients treated with AVYCAZ received a 33% lower daily dose than is currently recommended for patients with CrCl of 30 to less than or equal to 50 mL/min. Clinical cure rate in patients with normal renal function/mild renal impairment (CrCl greater than 50 mL/min) was 85% (322/379) with AVYCAZ plus metronidazole vs 86% (321/373) with meropenem, and clinical cure rate in patients with moderate renal impairment (CrCl 30 to less than or equal to 50 mL/min) was 45% (14/31) with AVYCAZ plus metronidazole vs 74% (26/35) with meropenem. The decreased clinical response was not observed for patients with moderate renal impairment at baseline (CrCl 30 to less than or equal to 50 mL/min) in the Phase 3 cUTI trials or the Phase 3 HABP/VABP trial. Monitor CrCl at least daily in patients with changing renal function and adjust the dosage of AVYCAZ accordingly.
  • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with AVYCAZ is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Exercise caution if this product is to be given to a penicillin or other beta-lactam-allergic patient because cross sensitivity among beta-lactam antibacterial drugs has been established. Discontinue the drug if an allergic reaction to AVYCAZ occurs.
  • Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including AVYCAZ, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial drugs. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible.
  • Seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment. Adjust dosing based on CrCl.
  • Prescribing AVYCAZ in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

ADVERSE REACTIONS

The most common adverse reactions in cIAI patients (≥ 5% when used with metronidazole) were diarrhea (8%), nausea (7%), and vomiting (5%). The most common adverse reactions in cUTI patients (3%) were diarrhea and nausea. The most common adverse reactions in HABP/VABP patients (≥ 5%) were diarrhea (15%) and vomiting (6%).