Open randomized study of cefepime versus piperacillin-gentamicin for treatment of febrile neutropenic cancer patients.

An open-label randomized trial comparing the efficacy and safety of cefepime versus piperacillin plus gentamicin (P+G) given intravenously for the treatment of febrile episodes in neutropenic patients with underlying malignancy was conducted at two oncology centers. Over a 30-month period 111 patients were enrolled and 99 patients were found to be suitable for evaluation. At the 72-h time of evaluation, cefepime monotherapy and P+G combination therapy produced comparable clinical response rates (78% for both). P+G and cefepime produced comparable response rates in microbiologically documented (78 versus 71%), clinically documented (100 versus 100%), and possible (75 versus 79%) infections. The P+G and cefepime treatments achieved comparable microbiological eradication of gram-negative (100 versus 71%) (P = 0.09) and gram-positive (44 versus 70%) (P = 0.37) organisms. There were no statistically significant differences in the rates of superinfection between the groups; however, more superinfections of fungal origin were noted in the P+G group. Cefepime was demonstrated to be an effective and safe treatment for febrile episodes in neutropenic patients with malignancies, and its lack of nephrotoxicity compared to P+G was noteworthy. Cefepime appears to be a candidate for monotherapy in febrile neutropenic cancer patients.

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1257. A phase II Prospective Randomized Study to Assess Ceftolozane-Tazobactam in the Management of Febrile Neutropenia in Patients with Hematological Malignancies

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1441 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S645-S645

Author(s):

Anne-Marie Chaftari ◽

Ray Y Hachem ◽

Alexandre Malek ◽

Victor Mulonovich ◽

Ariel D Szvalb ◽

...

Keyword(s):

High Risk ◽

Hematological Malignancies ◽

Antimicrobial Agents ◽

Randomized Study ◽

Bloodstream Infections ◽

Drug Discontinuation ◽

Open Label ◽

Gram Negative ◽

Material Support ◽

Neutropenic Patients

Abstract Background Despite the implementation of successful antibiotic stewardship programs, antibiotic resistance continue to emerge particularly against gram-negative bacteria. With the increase use of antibiotics in high risk patients with hematological malignancies, the empiric therapy with standard antibiotic could be inappropriate. New antibiotics may be useful to cover potential resistant pathogens. We evaluated the role of a new cephalosporin /β-lactamase inhibitor ceftolozane-tazobactam (C/T) in comparison to standard of care (SOC) antibiotics in the empiric treatment of febrile neutropenic cancer patients with hematological malignancies. Methods We conducted a prospective randomized open label comparative study to evaluate the safety and efficacy of C/T vs SOC antibiotics consisting of cefepime, piperacillin-tazobactam or meropenem when used in combination with gram positive antibacterial agents. Between May 2018 and March 2020, we enrolled 88 febrile neutropenic patients with hematological malignancies who presented to our emergency center. Patients received at least 72 hours of intravenous study drugs and were followed through end of IV therapy and for up to 42 days. Results A total of 88 patients were analyzed of whom 42 received C/T and 46 SOC antimicrobial agents. The rate of documented bloodstream infections was similar in both groups (CE-TZ 21% vs SOC 26%, p=0.61). Favorable clinical response at end of IV therapy was significantly better in the C/T arm compared to SOC therapy (88% vs 72%, p=0.039), at test of cure (21 days), and last follow-up (42 days). In patients with documented infections, the rate of microbiological eradication was similar in both groups. Drug-related adverse events that led to drug discontinuation was similar in both groups (7%). Similarly overall mortality was similar in both groups. Conclusion The empiric use of C/T to cover gram negative organisms in high risk febrile neutropenic patients with hematological malignancies is safe and associated with better clinical outcome than SOC antimicrobial agents. The emergence of resistant pathogens should be further evaluated. Disclosures Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

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Efficacy and safety of switching to pasireotide LAR monotherapy or in combination with pegvisomant in acromegaly patients controlled with combination therapy of somatostatin analogues and pegvisomant (PAPE study): a prospective, open-label 48 week study

Endocrine Abstracts ◽

10.1530/endoabs.56.gp4 ◽

2018 ◽

Author(s):

Eva C Coopmans ◽

Ammar Muhammad ◽

Joseph AMJL Janssen ◽

der Lely Aart J van ◽

Sebastian JCMM Neggers

Keyword(s):

Combination Therapy ◽

Somatostatin Analogues ◽

Efficacy And Safety ◽

Open Label

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Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

Pediatric Rheumatology ◽

10.1186/s12969-020-00488-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ekaterina Alexeeva ◽

Gerd Horneff ◽

Tatyana Dvoryakovskaya ◽

Rina Denisova ◽

Irina Nikishina ◽

...

Keyword(s):

Combination Therapy ◽

Controlled Trial ◽

Randomized Study ◽

Primary Objective ◽

Disease State ◽

Inactive Disease ◽

Open Label ◽

Standard Regimen ◽

Double Blind ◽

Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

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Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial

The Lancet Infectious Diseases ◽

10.1016/s1473-3099(20)30796-9 ◽

2020 ◽

Cited By ~ 5

Author(s):

Matteo Bassetti ◽

Roger Echols ◽

Yuko Matsunaga ◽

Mari Ariyasu ◽

Yohei Doi ◽

...

Keyword(s):

Gram Negative Bacteria ◽

Efficacy And Safety ◽

Open Label ◽

Phase 3 ◽

Gram Negative ◽

Carbapenem Resistant ◽

Serious Infections

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Study protocol for an open-label, single-arm, multicentre phase II trial to evaluate the efficacy and safety of combined triplet therapy and olanzapine for prevention of carboplatin-induced nausea and vomiting in gynaecological cancer patients

BMJ Open ◽

10.1136/bmjopen-2018-024357 ◽

2019 ◽

Vol 9 (1) ◽

pp. e024357

Author(s):

Hirotoshi Iihara ◽

Mototsugu Shimokawa ◽

Masakazu Abe ◽

Yoh Hayasaki ◽

Yukiyoshi Fujita ◽

...

Keyword(s):

Receptor Antagonist ◽

Cancer Patients ◽

Phase Ii ◽

Study Protocol ◽

Phase Ii Trial ◽

Emetogenic Chemotherapy ◽

Gynaecological Cancer ◽

Efficacy And Safety ◽

Open Label ◽

Multicentre Phase

IntroductionCarboplatin (CBDCA) administered at a dosage of 4 mg/mL/min or more area under the blood concentration-time curve (AUC) is considered to be ranked as the highest chemotherapy-induced nausea and vomiting (CINV) risk of the moderately emetogenic chemotherapy agents. The complete response (CR) rate for preventing overall CINV, defined as no emetic episodes and no use of rescue medication, for standard triplet antiemetic therapy (5-HT3RA, 5-hydroxytryptamine-3 receptor antagonist; NK1RA, neurokinin-1 receptor antagonist; DEX, dexamethasone) was approximately 60% in gynaecological cancer patients receiving CBDCA-based therapy. Further improvement in antiemetic treatment is needed to optimise care. This trial is to evaluate the efficacy and safety of using 5 mg olanzapine (OLZ) plus standard triplet antiemetic therapy for CINV after AUC ≥4 mg/mL/min CBDCA combination therapy in gynaecological cancer patients.Methods and analysisThis trial is an open-label, single-arm, multicentre phase II trial. Patients who receive CBDCA (AUC ≥4)-based therapy and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive OLZ (5 mg oral administration on days 1–4, after supper) in combination with 5-HT3RA, NK1RA and DEX. The primary endpoint is the CR rate during the overall period (0–120 hours). Testing the hypothesis that this regimen can improve CR rate from 60% (null hypothesis) to 75% (alternative hypothesis) with a one-sided type I error of 0.1 and power of 0.8 will require 53 patients. Considering the dropout rate, the target sample size is set at 60.Ethics and disseminationThe study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.Trial registration numberUMIN000031646.

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