Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00010307

Trial Description

start of 1:1-Block title

Title

A Multicenter, Randomized, Open-label Clinical Study of S-649266 or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

[---]*

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

This study is designed to provide evidence of efficacy of S-649266 in the treatment of
serious infections in adult patients caused by carbapenem-resistant Gram-negative pathogens.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

This study is designed to provide evidence of efficacy of S-649266 in the treatment of
serious infections in adult patients with either hospital acquired pneumonia
(HAP)/ventilator associated pneumonia (VAP)/healthcare-associated pneumonia (HCAP),
complicated urinary tract infection (cUTI), or bloodstream infections (BSI)/sepsis caused by
carbapenem-resistant Gram-negative pathogens.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00010307
  •   2016/04/14
  •   2016/02/26
  •   no
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2015-004703-23 
  •   NCT02714595  (ClinicalTrials.gov)
  •   1424R2131  (Shionogi)
  •   2015-004703-23 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Healthcare-associated Pneumonia (HCAP)
  •   Bloodstream Infections (BSI)
  •   Hospital Acquired Pneumonia (HAP)
  •   Complicated Urinary Tract Infection (cUTI)
  •   Sepsis
  •   Ventilator Associated Pneumonia (VAP)
  •   J18 -  Pneumonia, organism unspecified
  •   A41.9 -  Sepsis, unspecified
  •   N39.0 -  Urinary tract infection, site not specified
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Drug: S-649266
  •   Drug: Best Available Therapy
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- Clinical outcome per patient at test of cure (TOC) in patients with HAP/VAP/HCAP or BSI/sepsis; time frame: Test of cure, defined as 7 days after end of treatment (treatment duration is 7-14 days); For HAP/VAP/HCAP, clinical cure is defined as resolution or substantial improvement of baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no additional antibacterial therapy is required for the treatment of the current infection. For BSI/sepsis clinical cure is the resolution or substantial improvement of baseline signs and symptoms including a reduction in SOFA score, such that no additional antibacterial therapy is required for the treatment of BSI/sepsis.
- Microbiologic outcome (for Gram-negative pathogen) per patient at TOC in patients with cUTI; time frame: 7 days after end of treatment (7-14 days); Eradication is defined as a urine culture showing that the baseline Gram-negative uropathogen found at entry at ≥ 10^5 colony forming units (CFU)/mL are reduced to < 10^4 CFU/mL.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- Clinical outcome per patient at end of treatment (EOT) (HAP/VAP/HCAP or BSI/sepsis); time frame: End of treatment (7-14 days)
- Clinical outcome per pathogen at EOT and TOC (HAP/VAP/HCAP or BSI/sepsis); time frame: End of treatment (7-14 days), and 7 days after end of treatment
- Clinical outcome per patient/pathogen at EOT and TOC (cUTI); time frame: End of treatment (7-14 days) and 7 days after end of treatment
- Microbiologic outcome (for Gram-negative pathogen) per patient/pathogen at EOT, TOC, and follow-up (FUP) (HAP/VAP/HCAP or BSI/sepsis); time frame: End of treatment, 7 days after end of treatment and 14 days after end of treatment (follow-up)
- Microbiologic outcome (for Gram-negative pathogen) per patient at EOT, and FUP (cUTI); time frame: End of treatment (7-14 days) and 14 days after end of treatment
- Microbiologic outcome (for Gram-negative pathogen) per pathogen at EOT, TOC, and FUP (cUTI); time frame: End of treatment (7-14 days) and at 7 days and 14 days after end of treatment
- Microbiologic outcome with documented carbapenem-resistant Gram-negative bacteremia (regardless of primary infection diagnosis) at EOT, TOC, and FUP; time frame: End of treatment (7-14 days) and at 7 days and 14 days after end of treatment
- Participants with positive clinical and microbiologic outcome at EOT and TOC (cUTI only); time frame: End of treatment (7-14 days) and 7 days after end of treatment
- All-cause mortality at Day 14 and Day 28 for HAP/VAP/HCAP and BSI/sepsis; time frame: Day 14 and Day 28
- Composite endpoint of survival and no change in antibiotic treatment due to either lack of therapeutic benefit or drug-related toxicity at TOC; time frame: 7 days after end of treatment (7-14 days)
- Survival time (HAP/VAP/HCAP, BSI/sepsis); time frame: Up to 28 days after the end of treatment (7-14 days)
- Clinical Pulmonary Infection Score (CPIS) at EOT and TOC (HAP/VAP/HCAP only); time frame: End of treatment (7-14 days) and 7 days after end of treatment
- Sequential Organ Failure Assessment (SOFA) score at EOT and TOC; time frame: End of treatment and 7 days after end of treatment
- Number of participants with adverse events; time frame: From Baseline to 28 days after end of treatment (7-14 days); Safety and tolerability profile

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Croatia
  •   Germany
  •   Israel
  •   Italy
  •   Japan
  •   Korea, Republic of
  •   Taiwan, Province of China
  •   United States
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2016/03/31
  •   150
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

- Patients with clinically documented infection (HAP/VAP/HCAP, cUTI, or BSI/sepsis)
caused by a Gram-negative pathogen with evidence of carbapenem resistance

- Patients who have been treated previously with an empiric antibiotic other than the
study medications, but failed treatment, both clinically and microbiologically, are
eligible for the study if they have an identified pathogen which is non-susceptible
to the empiric treatment and is a carbapenem-resistant Gram-negative pathogen before
entering this study

- Male patients who are sterile or who agreed to use an appropriate method of
contraception (including use of a condom with spermicide) from Screening up to 28
days after EOT or according to country specific requirements, whichever is longer

- Female patients who are surgically sterile by hysterectomy and/or bilateral
oophorectomy with appropriate documentation of such surgery, are postmenopausal
(defined as cessation of regular menstrual periods for 2 years or more and confirmed
by a follicle-stimulating hormone test), or females of childbearing potential who
agree to use barrier contraception (including condom, diaphragm, or cervical cap)
with spermicide or who agree to use a highly effective method of contraception
(including contraceptive implant, injectable contraceptive, combination oral
contraceptive, intrauterine contraceptive device, and vasectomized partner) from
Screening up to 28 days after EOT or according to country specific requirements,
whichever is longer

- Patients meeting specific criteria for each infection site

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1. Patients who have a documented history of any moderate or severe hypersensitivity or
allergic reaction to any β-lactam (Note: for β-lactams, a history of a mild rash
followed by uneventful re-exposure is not a contraindication to enrollment)

2. Patients who need more than 3 systemic antibiotics as part of best available therapy
(BAT) for the treatment of the Gram-negative infection (Patients with mixed
Gram-positive or anaerobic infections may receive appropriate concomitant narrow
spectrum antibiotics [eg, vancomycin, linezolid, metronidazole, clindamycin])

3. Patients with co-infection caused by invasive aspergillosis, mucormycosis or other
highly lethal mold

4. Patients who have central nervous system (CNS) infection (eg, meningitis, brain
abscess, shunt infection)

5. Patients with infection requiring > 3 weeks of antibiotic treatment (eg, bone and
joint infection, endocarditis)

6. Patients with cystic fibrosis or bronchiectasis

7. Patients in refractory septic shock defined as persistent hypotension despite
adequate fluid resuscitation or vasopressive therapy at the time of randomization

8. Patients with severe neutropenia, ie, white blood cell (WBC) < 100 cells/μL

9. Female patients who have a positive pregnancy test at screening or who are lactating

10. Patients with acute physiology and chronic health evaluation II (APACHE II) > 30

11. Patients who have received potentially effective antibiotic therapy for the
carbapenem-resistant Gram-negative infections for a continuous duration of more than
24 hours in cUTI, 36 hours in HAP/VAP/HCAP or BSI/sepsis during the previous 72 hours
prior to randomization

12. Patients with any condition or circumstance that, in the opinion of the investigator,
would compromise the safety of the patient or the quality of the study data

13. Patients requires continuing treatment with methotrexate, procainamide, or probenecid

14. Patients who have received another investigational drug or device within 30 days
prior to study entry

15. Patients who have previously been randomized in this study or received S-649266

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Shionogi
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Shionogi
    • Shionogi Clinical Trials Administrator Clinical Support Help Line 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Shionogi Clinical Trials Administrator Clinical Support Help Line 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting planned
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2016/07/17


* This entry means the parameter is not applicable or has not been set.