Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)
NCT ID: NCT02655419
Last Updated: 2020-04-02
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
40 participants
INTERVENTIONAL
2016-05-19
2017-10-26
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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ATM-AVI + Metronidazole
Aztreonam-avibactam + metronidazole
ATM-AVI
Cohort 1:
(Creatinine clearance \> 50 mL/min)6500mg ATM/1777mg AVI on day 1 followed by total daily dose of 6000mg ATM/1640mg AVI
Cohorts 2 and 3:
(Creatinine clearance \> 50 mL/min) As above, or: 6500 mg ATM/2167 mg on Day 1 followed by a total daily dose of 6000 mg ATM/2000 m AVI
(Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1162 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/820 mg AVI, or:
4250 mg ATM/1417 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/1000 mg AVI
Metronidazole
Metronidazole 500mg infused over 1 hour every 8 hours
Interventions
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ATM-AVI
Cohort 1:
(Creatinine clearance \> 50 mL/min)6500mg ATM/1777mg AVI on day 1 followed by total daily dose of 6000mg ATM/1640mg AVI
Cohorts 2 and 3:
(Creatinine clearance \> 50 mL/min) As above, or: 6500 mg ATM/2167 mg on Day 1 followed by a total daily dose of 6000 mg ATM/2000 m AVI
(Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1162 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/820 mg AVI, or:
4250 mg ATM/1417 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/1000 mg AVI
Metronidazole
Metronidazole 500mg infused over 1 hour every 8 hours
Eligibility Criteria
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Inclusion Criteria
2. Male or female from 18 to 90 years
3. Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met
4. Diagnosis of cIAI
EITHER:
Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry
5. Patients who failed prior antibacterial treatment for their current cIAI can be enrolled but must:
* Have a known or suspected pathogen causing cIAI that is resistant to the prior therapy
* Require surgical intervention.
6. Patient must have or will have a surgical intervention within 24 hours (before or after) the administration of the first dose of study drug
Exclusion Criteria
2. Patient has been previously enrolled in this study, previously treated with ATM-AVI or previously participated in an investigational study containing AVI
3. Patient has participated or intends to participate in any other clinical study that involves the administration of a study drug during the course of the study, or during the 30 days prior to study start.
4. History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs
5. Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery within 24 hours of diagnosis primary etiology is not likely to be infectious
6. Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess or ischaemic/necrotic intestine without perforation
7. Staged abdominal repair (STAR), open abdomen technique or where infection source control is not likely to be achieved; unlikely to solely respond to antimicrobial therapy
8. Infection due to a pathogen that is unlikely to respond to ATM-AVI plus metronidazole
9. Rapidly progressive or terminal illness
10. Systemic antibacterial agents received within the 72- hour period prior to study entry, unless:
1. A new infection and no more than 24 hours of prior antibiotic treatment received within the 72 hour period prior to study entry or
2. Patient is considered to have failed the previous treatment
11. Concurrent infection that may interfere with the evaluation of clinical cure for the study therapy
12. requirement for effective concomitant systemic antibacterials or antifungals
13. Creatinine clearance ≤30 ml/min or requirement for renal replacement therapy
14. Acute hepatitis in the prior 6 months, chronic hepatitis, cirrhosis, acute hepatic failure, or acute decompensation of chronic hepatic failure
15. Hepatic disease as indicated by AST or ALT \>3 × ULN. Patients with AST and/or ALT \>3 × ULN and \< 5 × ULN are eligible if acute, not accompanied by a total bilirubin ≥ 2xULN and documented by the investigator as being directly related to cIAI.
16. Patient has a total bilirubin \>3 × ULN, unless isolated hyperbilirubinemia is directly related to cIAI or due to known Gilbert's disease
17. ALP \>3 × ULN. Patients with values \>3 × ULN and \<5 x ULN are eligible if acute and directly related to the infectious process being treated.
18. Immunocompromising illness
19. Active Clostridium difficile associated diarrhoea
20. Any other condition that may confound the results of the study or pose additional risks
21. Do not resuscitate order
22. Absolute neutrophil count \<1000/μL
23. Hematocrit \<25% or hemoglobin \<8 gm/dL.
24. Platelet count \<75,000/μL.
25. Currently receiving probenecid.
26. Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.
27. Unlikely to comply with protocol,
28. Currently receiving anti-convulsant therapy to prevent recurrence of a past history of seizures.
29. Prior liver, pancreas or small-bowel transplant.
18 Years
90 Years
ALL
No
Sponsors
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Innovative Medicines Initiative
OTHER
Pfizer
INDUSTRY
Responsible Party
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Principal Investigators
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Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Oliver Cornely
Role: PRINCIPAL_INVESTIGATOR
Clinical Trials Centre Cologne
Locations
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University Hospital C.
Lille, , France
CHU Limoges
Limoges, , France
Universitaetsklinikum Koeln Innere Medizin I
Cologne, , Germany
Universitaetsklinikum Schleswig-Holstein, Klinik fuer Infektiologie und Mikrobiologie, DZIF-CTU
Lübeck, , Germany
Hospital Universitario Cruces
Barakaldo, Bizkaia, Spain
Hospital Universitario Son Espases
Palma de Mallorca, ISLA Baleares, Spain
Hospital Universitari del Mar
Barcelona, , Spain
Hospital Universitario Reina Sofia
Córdoba, , Spain
Hospital Universitario Virgen Macarena
Seville, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Hospital Universitario Mutua de Tarrasa
Terrassa, , Spain
Countries
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References
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Das S, Riccobene T, Carrothers TJ, Wright JG, MacPherson M, Cristinacce A, McFadyen L, Xie R, Luckey A, Raber S. Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation. Eur J Clin Pharmacol. 2024 Apr;80(4):529-543. doi: 10.1007/s00228-023-03609-x. Epub 2024 Jan 22.
Jimenez-Rodriguez RM, Martin-Gutierrez G, Jimenez-Jorge S, Rosso-Fernandez CM, Tallon-Aguilar L, Roca-Oporto C, Padillo J, Luckey A, Cano A, Lopez-Ruiz J, Gomez-Zorrilla S, Bonnin-Pascual J, Boix-Palop L, Montejo JM, Torre-Cisneros J, Cisneros JM. Factors associated with recruitment success in the phase 2a study of aztreonam-avibactam development programme: a descriptive qualitative analysis among sites in Spain. BMJ Open. 2022 Feb 3;12(2):e051187. doi: 10.1136/bmjopen-2021-051187.
Cornely OA, Cisneros JM, Torre-Cisneros J, Rodriguez-Hernandez MJ, Tallon-Aguilar L, Calbo E, Horcajada JP, Queckenberg C, Zettelmeyer U, Arenz D, Rosso-Fernandez CM, Jimenez-Jorge S, Turner G, Raber S, O'Brien S, Luckey A; COMBACTE-CARE consortium/REJUVENATE Study Group. Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study. J Antimicrob Chemother. 2020 Mar 1;75(3):618-627. doi: 10.1093/jac/dkz497.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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To obtain contact information for a study center near you, click here.
Other Identifiers
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C3601001
Identifier Type: OTHER
Identifier Source: secondary_id
2015-002726-39
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
D4910C00009
Identifier Type: -
Identifier Source: org_study_id
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