A Phase 3 Randomized, Double-Blind Study of Ceftobiprole Medocaril versus Linezolid Plus Ceftazidime in the Treatment of Nosocomial Pneumonia - CHOPIN-1

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2005-004174-24-CZ
• Date of registration: 10/07/2006
• Prospective Registration: Yes
• Primary sponsor: Johnson&Johnson Pharmaceutical Research&Development, L.L.C.
• Public title: A Phase 3 Randomized, Double-Blind Study of Ceftobiprole Medocaril versus Linezolid Plus Ceftazidime in the Treatment of Nosocomial Pneumonia - CHOPIN-1
• Scientific title: A Phase 3 Randomized, Double-Blind Study of Ceftobiprole Medocaril versus Linezolid Plus Ceftazidime in the Treatment of Nosocomial Pneumonia - CHOPIN-1
• Date of first enrolment: 24/08/2006
• Target sample size: 770
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004174-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent provided. Consent may be given for unconscious/incapacitated subjects by their next of kin, guardian, or legal representative according to local regulatory and ethical practice using a subject information sheet and informed consent form approved by the responsible Ethics Committee.
2. Male or female subjects aged =18 years
3. Female subjects must be postmenopausal (for at least 1 year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections or patch, intrauterine device, double-barrier method [e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], male partner sterilization or, at the discretion of the investigator, abstinence), before entry and throughout the study; and have a negative serum or urine pregnancy test (depending on local regulations) at screening.
4. Subjects suffering from NP or VAP defined as follows:
Nosocomial Pneumonia
(Subjects must have a, b, c, and d)
a) Clinical diagnosis of pneumonia after a minimum of 72 hours of hospitalization or in a chronic care facility
Exceptions would include:
– =48 to <72 hours of hospitalization or in a chronic care facility, if at admission no acute inflammatory pulmonary infiltrate was present, WBC and differential blood count was normal, and the reason for admission was not an infection, OR
– discharge from hospital or chronic care facility =48 hours after a stay of =72 hours.
b) Clinical signs or symptoms of pneumonia with AT LEAST 2 of the following criteria:
• New onset of purulent sputum production or respiratory secretions or a worsening in character of sputum.
• Tachypnea (respiratory rate =20/minute), particularly if progressive in nature.
• Hypoxemia with a P02=60 mmHg while subject is breathing on room air, as determined by pulse oximetry or arterial blood gas, or alveolar arterial O2 gradient, or respiratory failure requiring mechanical ventilation.
c) New or persistent (persistence is defined as the infiltrate being radiographically visible for at least 72 hours) radiographic infiltrates (not related to another disease process)
d) Fever or leukocytosis/leukopenia consistent with a diagnosis of pneumonia with AT
LEAST 1 of the following:
• Fever ([in the absence of antipyretics], increase in core temperature of >1°C OR an oral temperature >38°C, a tympanic temperature >38.5°C, a rectal/core temperature >39°C, OR hypothermia, defined as a rectal/core body temperature of <35°C).
• Leukocytosis (a total WBC count =10 x 109/L or =15% immature neutrophils [bands], regardless of total peripheral white count; or leukopenia with total WBC =4.5 x 109/L).
5. Microbiological samples (respiratory secretions) suitable for culture and microscopy
6. APACHE II score =8 and =25
7. Subjects with NP (as defined above) who developed pneumonia more than 48 hours after onset of mechanical ventilation.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Female subjects who are pregnant or lactating.
2. Known or suspected hypersensitivity to any related anti-infective (including ß-lactam antibiotics such as penicillins, cephalosporins, oxazolidinones, or monobactams)
3. Any known or suspected condition or concurrent treatment that would be contraindicated by the prescribing information for linezolid (any medicinal product which inhibits monoamine oxidases A or B, [e.g., phenelzine, isocarboxazid, selegiline, moclobemide] or within 2 weeks of taking any such medicinal product) or ceftazidime.
Exception: Subjects with underlying conditions and/or on concomitant medications that might put them at risk from MAO inhibition can only be enrolled if they are hospitalized.
4. Known or suspected severe renal impairment, (calculated creatinine clearance [CrCl] <30 mL/minute or oliguria <20 mL/hour unresponsive to fluid challenge) or any form of dialysis.
5. Known or suspected hepatic dysfunction (total bilirubin, or alanine aminotransferase [ALT], or aspartate aminotransferase [AST] =3 times upper limit of the normal range [ULN]).
6. QTcB (Bazett’s correction) >450 msec at baseline
7. Previous enrollment in this study.
8. Treatment with any investigational drug within 30 days before enrollment.
9. Any other known or suspected condition of the subject that may jeopardize adherence to protocol requirements (e.g., severe chronic obstructive pulmonary disease [COPD], NYHA Class 4 cardiac disease, burn subjects with >15% total body burn or any significant third degree burn).
10. Known to be HIV-positive with CD4 counts of =0.2x109/L (=200 cells/mm3). (Subjects with HIV and >0.2x109/L [>200 cells/mm3] may be included).
11. Presence of myelosuppression or neutropenia (absolute neutrophil count [ANC] =0.5x109/L [<500 PMNs/mm3]), severe anemia (hemoglobin <6.5 g/dL, or severe
thrombocytopenia (<49.9x109/cm). Note: subjects receiving immunosuppressive therapy who are expected to reach a nadir of <500 PMNs/mm3 during administration of study drug should not be enrolled.
12. Children or other family members of the investigator or of employees of the study center, with
direct involvement in the proposed study or other studies under the direction of that investigator or study center.
13. Sustained shock (e.g., systolic BP <90 mmHg for >2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents).
14. Subjects with either
- known bronchial obstruction or a history of postobstructive pneumonia (mild and moderate COPD subjects are allowed) including primary lung cancer or another malignancy metastatic to the lungs,
- cystic fibrosis,
- lung abscess,
- pleural effusion as a primary source of infection
- active tuberculosis, or
- subjects requiring antibiotic cover for aspiration pneumonia, atypical pneumonia (including Legionella pneumophila), or Pneumocystis jiroveci (carinii) pneumonia.
15. Systemic antimicrobial therapy for more than 24 hours in the 7 days prior to enrollment Exceptions: Systemic antimicrobial therapy for >24 hours is permitted in case of any of the following:
a) the infection is caused by microbiologically-confirmed pathogens that are resistant to the previous antimicrobial agents.
b) the subject is clinically deteriorating despite at least 72 hours of antibiotic therapy and is documented to be infected or colonized with a pathogen that is susceptible to both ceftobiprole and the comparator regimen.
c) the subject has received antibiotic th

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hospital-Acquired or Nosocomial Pneumonia

Intervention(s)

Product Name: Ceftobiprole
Product Code: BAL 5788
Pharmaceutical Form: Powder for solution for infusion
CAS Number: 252188-71-9
Current Sponsor code: BAL5788
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Biotum
Product Name: Biotum
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Ceftazidime
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Zyvox
Product Name: Zyvox
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Linezolid
CAS Number: 165800-03-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Ceftazidime EG
Product Name: Ceftazidime EG
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: ceftazidime
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Primary end point(s): Clinical cure rate, defined as the ratio of the number of clinically cured
subjects to the total number of subjects in the population, at TOC visit

Main Objective: Clinical cure rate, defined as the ratio of the number of clinically cured subjects to the total number of subjects in the population at TOC visit.

Secondary Objective: Microbiological eradication rate at TOC visit
• Clinical cure rate and microbiological relapse at LFU visit
• Thirty-day pneumonia-specific mortality rates (all deaths due to pneumonia within 30 days after randomization)
• Thirty-day all-cause mortality rates (all deaths within 30 days after randomization)
• Time to clinical cure.
• Time to microbiological eradication.
• Duration of treatment.
• Clinical cure rate and microbiological eradication rates in VAP subjects
• Medical Resource Utilization data

Secondary ID(s)

BAP00248

Ethics review

Status: Approved
Approval date: 08/02/2006
Contact:

Results

• Results available: Yes
• Date Posted: 25/10/2017
• Date Completed: 17/05/2007
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-004174-24/results