Randomised clinical trial of moxifloxacin versus ertapenem in complicated intra-abdominal infections: results of the PROMISE study

Waele, Jan J. De; Tellado, Jose M.; Alder, Jeff; Reimnitz, Peter; Jensen, Markus; Hampel, Barbara; Arvis, Pierre

doi:10.1016/j.ijantimicag.2012.08.013

Cited by 21 publications

(35 citation statements)

References 30 publications

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“…Of the four randomized controlled trials (conducted between 2000 and 2009), three were double-blind [13,[15][16] and one study was open-label [14]. All studies were designed to demonstrate the non-inferiority of moxifloxacin to comparator antibiotic regimens and used a non-inferiority margin of either 10% [13][14]16] or 15% [15].…”

Section: Design Of Studies Used In the Analysismentioning

confidence: 99%

“…All studies were designed to demonstrate the non-inferiority of moxifloxacin to comparator antibiotic regimens and used a non-inferiority margin of either 10% [13][14]16] or 15% [15]. All four studies were performed in accordance with the Declaration of Helsinki, the rules of International Conference on Harmonization (ICH) Good Clinical Practice and relevant national guidelines.…”

Section: Design Of Studies Used In the Analysismentioning

confidence: 99%

“…Independent Ethics Committees approved the respective study protocols and written consent prior to enrollment from all patients in each study was obtained. The main regions enrolling patients in these studies were the United States [13], Asia [15], and Europe [14,16]. The clinical diagnoses were described in detail in the clinical study protocol and approved by regulatory authorities prior to the initiation of the studies in each individual study.…”

Section: Design Of Studies Used In the Analysismentioning

confidence: 99%

“…Eligible patients were adults ( ‡ 18 y) with a primary diagnosis of cIAI that was supported by radiologic evidence of gastrointestinal tract perforation and required surgical intervention by laparotomy or laparoscopy [13][14][15][16] or percutaneous aspiration [13][14][15] for source control in addition to IV antibiotic therapy. Patients also had evidence of gross peritoneal inflammation with purulent exudates into the peritoneal cavity.…”

Section: Inclusion Criteriamentioning

confidence: 99%

“…On the basis of pooled data from the four Phase III randomized, active-controlled, prospective clinical trials [13][14][15][16] comparing the efficacy and safety of moxifloxacin monotherapy with that of comparator regimens in mild-to-moderate cIAIs, we undertook a retrospective analysis of the efficacy and safety of moxifloxacin in this subgroup of patients with secondary peritonitis, reflecting an advanced form of peritonitis.…”

mentioning

confidence: 99%

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Efficacy and Safety of Moxifloxacin in Hospitalized Patients with Secondary Peritonitis: Pooled Analysis of Four Randomized Phase III Trials

Waele

Tellado²,

Weiß³

et al. 2014

Surgical Infections

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Background: Secondary peritonitis is an advanced form of complicated intra-abdominal infection (cIAI) requiring hospitalization, surgical source control, and empiric antibiotic therapy against causative aerobic and anaerobic bacteria.Methods: This pooled analysis of four prospective, active-controlled randomized clinical trials compared the efficacy and safety of moxifloxacin with that of comparator antibiotics in patients with confirmed secondary peritonitis. The primary efficacy endpoint was clinical success rate at test-of-cure (TOC) between day 10 and 45 post-therapy in the per-protocol (PP) population. Safety and clinical efficacy were assessed also in the intent-totreat population (ITT). Bacteriological success was assessed at TOC in the microbiologically-valid population as a secondary efficacy endpoint. Results: Overall clinical success rates at TOC were 85.3% (431 of 505 patients) in the moxifloxacin and 88.4% (459 of 519 patients) in the comparator treatment groups (PP population, point estimate for the difference in success rates: -3.0%; 95% CI -7.06%, 1.05%), respectively. Similar clinical success rates between moxifloxacin and comparators were observed by anatomical site of infection, and ranged from 80.6% to 100% for moxifloxacin and from 71.4% to 96.6% for comparators, respectively. Bacteriologic success rates were similar with moxifloxacin (82.4%) and comparators (86.8%), respectively. The proportion of patients experiencing any treatment-emergent adverse events was slightly higher with moxifloxacin (67.3%) versus comparators (59.8%). Rates of drug-related adverse events (20.9% versus 20.0%) and deaths (4.3% versus 3.4%) were similar in moxifloxacin and comparator groups; none of the deaths were drug-related. Conclusions: The data suggests that once-daily IV (or IV/PO) moxifloxacin has a comparable efficacy and safety profile to antibiotic regimens approved previously in the subgroup of patients with secondary peritonitis of mild-to-moderate severity.

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Section: Design Of Studies Used In the Analysismentioning

confidence: 99%

Section: Design Of Studies Used In the Analysismentioning

confidence: 99%

Section: Design Of Studies Used In the Analysismentioning

confidence: 99%

Section: Inclusion Criteriamentioning

confidence: 99%

mentioning

confidence: 99%

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Efficacy and Safety of Moxifloxacin in Hospitalized Patients with Secondary Peritonitis: Pooled Analysis of Four Randomized Phase III Trials

Waele

Tellado²,

Weiß³

et al. 2014

Surgical Infections

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Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis

Sippola

Haijanen

Grönroos

et al. 2021

JAMA

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IMPORTANCEAntibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known.OBJECTIVE To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis. DESIGN, SETTING, AND PARTICIPANTSThe Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019.INTERVENTIONS Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days. MAIN OUTCOMES AND MEASURESThe primary end point was treatment success (Ն65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference. RESULTS Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ϱ) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ϱ) for patients treated with intravenous followed by oral antibiotics. The difference was −3.6% ([1-sided 95% CI, −9.7% to ϱ]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin.CONCLUSION AND RELEVANCE Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics.

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Application of Physiologically‐Based and Population Pharmacokinetic Modeling for Dose Finding and Confirmation During the Pediatric Development of Moxifloxacin

Willmann

Frei

Sutter

et al. 2019

CPT Pharmacom & Syst Pharma

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Moxifloxacin is a widely used fluoroquinolone for the treatment of complicated intra‐abdominal infections. We applied physiologically‐based pharmacokinetic (PBPK) and population pharmacokinetic (popPK) modeling to support dose selection in pediatric patients. We scaled an existing adult PBPK model to children based on prior physiological knowledge. The resulting model proposed an age‐dependent dosing regimen that was tested in a phase I study. Refined doses were then tested in a phase III study. A popPK analysis of all clinical pediatric data confirmed the PBPK predictions, including the proposed dosing schedule in children, and supported pharmacokinetics‐related safety/efficacy questions. The pediatric PBPK model adequately predicted the doses necessary to achieve antimicrobial efficacy while maintaining safety in the phase I and III pediatric studies. Altogether, this study retroactively demonstrated the robustness and utility of modeling to support dose finding and confirmation in pediatric drug development for moxifloxacin.

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Randomised clinical trial of moxifloxacin versus ertapenem in complicated intra-abdominal infections: results of the PROMISE study

Cited by 21 publications

References 30 publications

Efficacy and Safety of Moxifloxacin in Hospitalized Patients with Secondary Peritonitis: Pooled Analysis of Four Randomized Phase III Trials

Efficacy and Safety of Moxifloxacin in Hospitalized Patients with Secondary Peritonitis: Pooled Analysis of Four Randomized Phase III Trials

Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis

Application of Physiologically‐Based and Population Pharmacokinetic Modeling for Dose Finding and Confirmation During the Pediatric Development of Moxifloxacin

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