Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)

NCT02655419

Last updated date
Study Location
University Hospital C.
Lille Cedex, , 59037, France
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Complicated Intra-Abdominal Infections, cIAIs
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-90 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. Provision of informed consent

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


1. Involvement in the planning and/or conduct of the study


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.

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Complicated Intra-Abdominal Infections, cIAIsDetermine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE) NCT02655419
  1. Lille Cedex,
  2. Limoges cedex,
  3. Koeln,
  4. Luebeck,
  5. Barakaldo, Bizkaia
  6. Palma de Mallorca, ISLA Baleares
  7. Barcelona,
  8. Cordoba,
  9. Sevilla,
  10. Sevilla,
  11. Terrassa,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)
Official Title  ICMJE A PHASE IIA PROSPECTIVE, OPEN-LABEL, MULTICENTER STUDY TO DETERMINE THE PHARMACOKINETICS (PK) AND SAFETY AND TOLERABILITY OF AZTREONAM-AVIBACTAM (ATM-AVI) FOR THE TREATMENT OF COMPLICATED INTRA-ABDOMINAL INFECTIONS (CIAIS) IN HOSPITALIZED ADULTS
Brief Summary Determine the PK and safety and tolerability of aztreonam-avibactam (ATM-AVI) in the treatment of hospitalized adults with cIAI
Detailed Description A Phase IIa prospective, open-label, multicenter study to determine the pharmacokinetics (PK) and safety and tolerability of aztreonam-avibactam (ATM-AVI) for the treatment of complicated Intra-Abdominal Infections (cIAIs) in hospitalized adults.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Complicated Intra-Abdominal Infections, cIAIs
Intervention  ICMJE
  • Drug: 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

  • Drug: Metronidazole
    Metronidazole 500mg infused over 1 hour every 8 hours
Study Arms  ICMJE Experimental: ATM-AVI + Metronidazole
Aztreonam-avibactam + metronidazole
Interventions:
  • Drug: ATM-AVI
  • Drug: Metronidazole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 12, 2016)
40
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 26, 2017
Actual Primary Completion Date October 26, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provision of informed consent
  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:

  1. Involvement in the planning and/or conduct of the study
  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 ?-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/?L
  23. Hematocrit <25% or hemoglobin <8 gm/dL.
  24. Platelet count <75,000/?L.
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02655419
Other Study ID Numbers  ICMJE D4910C00009
C3601001 ( Other Identifier: Alias Study Number )
2015-002726-39 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Innovative Medicines Initiative (IMI) COMBACTE-CARE
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
Principal Investigator:Oliver CornelyClinical Trials Centre Cologne
PRS Account Pfizer
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP