Bacterial Infections
Conditions
Keywords
Registre MONTRAVERS
Brief summary
This study will describe clinical outcome and safety data collected prospectively in subjects hospitalized in an intensive care unit (ICU) presenting with an infection for which treatment with tigecycline, alone or in combination, is planned. Data will be collected only from subjects providing informed consent.
Detailed description
Healthcare visit. Extension Rationale: In order to perform the necessary corrective actions required and to secure database consistency, we request an extension for posting of Basic Results due 26-May-2011 for protocol 3074A1-4448 (B1811030), NCT00799591. Our proposed submission date is 14-Sept-2011. Pfizer acquired Wyeth on October 16, 2009. With regard to this study, our reconciliation of data identified some discrepancies in data listed in the Project database (managed by the CRO) and the Safety Database (managed by Pfizer). We are taking corrective action which involves: sending queries to investigators, collecting corrective signed forms, and implementing changes within the database. We are requesting this extension to complete that work so that the data can be treated as final and the CSR can be completed.
Interventions
OTHERObservational study so no intervention in the patient.
Observational study so no intervention in the patient.
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult men and women (18 years). * Subjects hospitalized in a medical or surgical intensive care unit (ICU) (on the day of enrolment in the study). * Subjects treated with tigecycline (first, second or third line), said treatment freely chosen by the participating physician, prior to enrollment in the study.
Exclusion criteria
* Subjects participating in another biomedical research study. * Patient (or legal representative) who has not dated or signed informed consent document.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at End of Treatment (EOT) | End of Treatment (on the day of last dose of study treatment) or up to 25 months | Clinical Success: lack of need to use new antibiotic or a surgical treatment not initially planned for initial infection. Failure: persistence of initial infection (required change of antibiotic or surgery), death related to infection (\>48 hours after start of treatment with tigecycline), or premature cessation of treatment due to treatment-related Adverse Event. Undetermined: insufficient data for assessment, death not directly related to initial infection, death within first 48 hours of start of treatment with tigecycline, or additional antibiotic treatment for other than initial infection. |
| Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at Follow-up Visit | Follow-up Visit (7 days after last dose or at hospital discharge whichever occurred within 7 days after last dose) or up to 25 months | Clinical Success: lack of need to use new antibiotic or a surgical treatment not initially planned for initial infection. Failure: persistence of initial infection (required change of antibiotic or surgery), death related to infection (\>48 hours after start of treatment with tigecycline), or premature cessation of treatment due to treatment-related Adverse Event. Undetermined: insufficient data for assessment, death not directly related to initial infection, death within first 48 hours of start of treatment with tigecycline, or additional antibiotic treatment for other than initial infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at EOT | Baseline (Inclusion), End of Treatment (on the day of last dose of study treatment) or up to 25 months | Combinations of antibiotic treatments for participants treated with clinical success with tigecycline. Clinical success defined as lack of need to use new antibiotic or a surgical treatment not initially planned for initial infection. |
| Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at Follow-up Visit | Baseline (Inclusion), Follow-up Visit (7 days after last dose or at hospital discharge whichever occurred within 7 days after last dose) or up to 25 months | Combinations of antibiotic treatments for participants treated with clinical success with tigecycline. Clinical success defined as lack of need to use new antibiotic or a surgical treatment not initially planned for initial infection. |
| Percentage of Participants Per Tigecycline Loading Dose and Maintenance Dose | Baseline (Inclusion) through last dose of study treatment or up to 25 months | Tigecycline powder for solution 50 milligrams (mg) for intravenous (IV) infusion could be administered with an initial loading dose of 100 mg followed by 50 mg administered IV (over 30 to 60 minutes) every 12 hours for 5 to 14 days. Use and dosage recommendations for tigecycline (Tygacil®) were on the basis of the approved Summary of Product Characteristics (SmPC) and adjusted solely according to medical and therapeutic necessity. |
| Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Direct Examination | Post-baseline (Day 1) through last dose of study treatment or up to 25 months | Microbiological sampling results categorized according to direct examination (identification of the class of germs). |
| Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Positive Blood Culture | Post-baseline (Day 1) through last dose of study treatment or up to 25 months | Microbiological sampling results categorized as a positive blood culture (presence of infection). |
| Mean Duration (Days) of Treatment With Tigecycline | Baseline (Inclusion) through last dose of study treatment or up to 25 months | — |
Countries
France
Participant flow
Recruitment details
This was a prospective observational study, non-comparative, conducted in 26 French Intensive Care Units (ICUs). Patients who were hospitalized in ICUs and presented with complicated infections of skin or soft tissues or complicated intra-abdominal infections and who met the inclusion criteria of the study were included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Tigecycline Use and dosage recommendations for tigecycline (Tygacil®) were on the basis of the approved Summary of Product Characteristics (SmPC) and adjusted solely according to medical and therapeutic necessity. Tigecycline powder for solution for intravenous (IV) infusion could be administered with an initial loading dose of 100 milligrams (mg) followed by 50 mg administered IV (over 30 to 60 minutes) every 12 hours for 5 to 14 days. | 156 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Antibiotic changed, no apparent reason | 1 |
| Overall Study | Death | 14 |
| Overall Study | De-escalation of doses | 20 |
| Overall Study | Infectious origin not probable | 1 |
| Overall Study | New infection | 4 |
| Overall Study | Persistance of fever undetermined origin | 1 |
| Overall Study | Resistance germ and technical failure | 2 |
| Overall Study | Resistant germ | 11 |
| Overall Study | Technical failure | 12 |
Baseline characteristics
| Characteristic | Tigecycline |
|---|---|
| Age Continuous | 60.1 years STANDARD_DEVIATION 15.4 |
| Mean Sepsis-related Organ Failure Assessment (SOFA) score | 7.0 scores on a scale STANDARD_DEVIATION 4.5 |
| Mean Simplified Acute Physiology Score II (SAPSII): Integer score | 43.3 scores on a scale STANDARD_DEVIATION 16.4 |
| Percentage of participants per co-morbid (concomitant) diseases Chronic hepatic failure Type A | 80.0 percentage of participants |
| Percentage of participants per co-morbid (concomitant) diseases Chronic hepatic failure Type C | 20.0 percentage of participants |
| Percentage of participants per co-morbid (concomitant) diseases Chronic renal failure | 10.3 percentage of participants |
| Percentage of participants per co-morbid (concomitant) diseases Diabetes mellitus | 5.1 percentage of participants |
| Percentage of participants per co-morbid (concomitant) diseases Immuno > 10%: Cancer | 53.8 percentage of participants |
| Percentage of participants per co-morbid (concomitant) diseases Immuno > 10%: Corticoids plus other Immuno | 15.4 percentage of participants |
| Percentage of participants per co-morbid (concomitant) diseases Immuno > 10%: Other Immuno | 13.5 percentage of participants |
| Percentage of participants per co-morbid (concomitant) diseases Immuno > 10%: Use of corticoids | 15.4 percentage of participants |
| Percentage of participants per co-morbid (concomitant) diseases Non-insulin dependent diabetes | 14.1 percentage of participants |
| Percentage of participants per reason for choice of treatment with Tigecycline Allergy or intolerance to other antiobiotics | 9.6 percentage of participants |
| Percentage of participants per reason for choice of treatment with Tigecycline Failure of previous treatment | 12.2 percentage of participants |
| Percentage of participants per reason for choice of treatment with Tigecycline MRB suspected or identified | 40.4 percentage of participants |
| Percentage of participants per reason for choice of treatment with Tigecycline Multiple sites | 15.4 percentage of participants |
| Percentage of participants per reason for choice of treatment with Tigecycline Other | 6.4 percentage of participants |
| Percentage of participants per reason for choice of treatment with Tigecycline Polymicrobial infection | 55.1 percentage of participants |
| Percentage of participants per reason for choice of treatment with Tigecycline Renal impairment | 17.9 percentage of participants |
| Percentage of participants per reason for choice of treatment with Tigecycline Rescue medication | 8.3 percentage of participants |
| Percentage of participants per type of infection: Infection of skin and soft tissue Dermo-panniculis | 96.6 percentage of participants |
| Percentage of participants per type of infection: Infection of skin and soft tissue Infection: Community | 31.0 percentage of participants |
| Percentage of participants per type of infection: Infection of skin and soft tissue Infection: Nosocomial | 69.0 percentage of participants |
| Percentage of participants per type of infection: Infection of skin and soft tissue Localization ≥ 10%: Abdomen | 52.9 percentage of participants |
| Percentage of participants per type of infection: Infection of skin and soft tissue Localization ≥ 10%: Head and neck | 29.4 percentage of participants |
| Percentage of participants per type of infection: Infection of skin and soft tissue Localization ≥ 10%: Perineum | 11.8 percentage of participants |
| Percentage of participants per type of infection: Intra-abdominal Infection: Community | 30.7 percentage of participants |
| Percentage of participants per type of infection: Intra-abdominal Infection: Nosocomial | 69.3 percentage of participants |
| Percentage of participants per type of infection: Intra-abdominal Localization ≥ 10%: Colon | 37.5 percentage of participants |
| Percentage of participants per type of infection: Intra-abdominal Localization ≥ 10%: Other | 12.5 percentage of participants |
| Percentage of participants per type of infection: Intra-abdominal Peritonitis: Abscess without peritonitis | 22.1 percentage of participants |
| Percentage of participants per type of infection: Intra-abdominal Peritonitis: Generalized | 63.2 percentage of participants |
| Percentage of participants per type of infection: Intra-abdominal Peritonitis: Localized | 14.7 percentage of participants |
| Percentage of participants per type of infection: Other infections Infection: Nosocomial | 89.3 percentage of participants |
| Percentage of participants per type of infection: Other infections Infections: Community | 10.7 percentage of participants |
| Percentage of participants per type of infection: Other infections Localization ≥ 10%: Lung | 67.9 percentage of participants |
| Percentage of participants per type of infection: Other infections Localization ≥ 10%: Miscellaneous | 32.1 percentage of participants |
| Percentage of participants with antibiotic treatment(s) taken 30 days prior to Tigecycline treatment Treatment within 30 days prior=No | 7.1 percentage of participants |
| Percentage of participants with antibiotic treatment(s) taken 30 days prior to Tigecycline treatment Treatment within 30 days prior=Yes | 92.9 percentage of participants |
| Percentage of participants with microbiological sampling results: direct examination Gram negative bacilli | 59.8 percentage of participants |
| Percentage of participants with microbiological sampling results: direct examination Gram positive cocci | 47.1 percentage of participants |
| Percentage of participants with microbiological sampling results: direct examination Polymicrobial | 33.3 percentage of participants |
| Percentage of participants with microbiological sampling results: positive blood culture | 11.7 percentage of participants |
| Sex: Female, Male Female | 56 Participants |
| Sex: Female, Male Male | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 156 |
| serious Total, serious adverse events | 26 / 156 |
Outcome results
Primary
Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at End of Treatment (EOT)
Clinical Success: lack of need to use new antibiotic or a surgical treatment not initially planned for initial infection. Failure: persistence of initial infection (required change of antibiotic or surgery), death related to infection (\>48 hours after start of treatment with tigecycline), or premature cessation of treatment due to treatment-related Adverse Event. Undetermined: insufficient data for assessment, death not directly related to initial infection, death within first 48 hours of start of treatment with tigecycline, or additional antibiotic treatment for other than initial infection.
Time frame: End of Treatment (on the day of last dose of study treatment) or up to 25 months
Population: Intent-to-Treat (ITT): all participants included in the study who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at End of Treatment (EOT) | Success | 59.6 percentage of participants |
| Tigecycline | Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at End of Treatment (EOT) | Clinical Failure - deaths | 2.6 percentage of participants |
| Tigecycline | Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at End of Treatment (EOT) | Clinical Failure - other criteria | 15.4 percentage of participants |
| Tigecycline | Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at End of Treatment (EOT) | Undetermined | 22.4 percentage of participants |
Primary
Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at Follow-up Visit
Clinical Success: lack of need to use new antibiotic or a surgical treatment not initially planned for initial infection. Failure: persistence of initial infection (required change of antibiotic or surgery), death related to infection (\>48 hours after start of treatment with tigecycline), or premature cessation of treatment due to treatment-related Adverse Event. Undetermined: insufficient data for assessment, death not directly related to initial infection, death within first 48 hours of start of treatment with tigecycline, or additional antibiotic treatment for other than initial infection.
Time frame: Follow-up Visit (7 days after last dose or at hospital discharge whichever occurred within 7 days after last dose) or up to 25 months
Population: ITT population; N=number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at Follow-up Visit | Success | 53.1 percentage of participants |
| Tigecycline | Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at Follow-up Visit | Clinical Failure | 22.1 percentage of participants |
| Tigecycline | Percentage of Participants Per Clinical Outcome (Success, Failure, or Undetermined) at Follow-up Visit | Undetermined | 24.8 percentage of participants |
Secondary
Mean Duration (Days) of Treatment With Tigecycline
Time frame: Baseline (Inclusion) through last dose of study treatment or up to 25 months
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tigecycline | Mean Duration (Days) of Treatment With Tigecycline | 10.2 days | Standard Deviation 8.8 |
Secondary
Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at EOT
Combinations of antibiotic treatments for participants treated with clinical success with tigecycline. Clinical success defined as lack of need to use new antibiotic or a surgical treatment not initially planned for initial infection.
Time frame: Baseline (Inclusion), End of Treatment (on the day of last dose of study treatment) or up to 25 months
Population: ITT population; N=number of participants treated with combinations of antibiotics with analyzable data at observation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at EOT | Aminoglycosides | 22.6 percentage of participants |
| Tigecycline | Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at EOT | Aminoglycosides: Amikacin | 14.0 percentage of participants |
| Tigecycline | Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at EOT | Penicillins | 15.1 percentage of participants |
| Tigecycline | Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at EOT | Penicillins: Piperacillin / Tazobactam | 9.7 percentage of participants |
Secondary
Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at Follow-up Visit
Combinations of antibiotic treatments for participants treated with clinical success with tigecycline. Clinical success defined as lack of need to use new antibiotic or a surgical treatment not initially planned for initial infection.
Time frame: Baseline (Inclusion), Follow-up Visit (7 days after last dose or at hospital discharge whichever occurred within 7 days after last dose) or up to 25 months
Population: ITT population; N=number of participants treated with combinations of antibiotics with analyzable data at observation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at Follow-up Visit | Aminoglycosides | 23.4 percentage of participants |
| Tigecycline | Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at Follow-up Visit | Aminoglycosides: Amikacin | 14.3 percentage of participants |
| Tigecycline | Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at Follow-up Visit | Penicillins | 15.6 percentage of participants |
| Tigecycline | Percentage of Participants (> 10%) With Use of Other Antibiotics in Combination With Tigecycline Who Had Clinical Success at Follow-up Visit | Penicillins: Piperacillin / Tazobactam | 10.4 percentage of participants |
Secondary
Percentage of Participants Per Tigecycline Loading Dose and Maintenance Dose
Tigecycline powder for solution 50 milligrams (mg) for intravenous (IV) infusion could be administered with an initial loading dose of 100 mg followed by 50 mg administered IV (over 30 to 60 minutes) every 12 hours for 5 to 14 days. Use and dosage recommendations for tigecycline (Tygacil®) were on the basis of the approved Summary of Product Characteristics (SmPC) and adjusted solely according to medical and therapeutic necessity.
Time frame: Baseline (Inclusion) through last dose of study treatment or up to 25 months
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Percentage of Participants Per Tigecycline Loading Dose and Maintenance Dose | Loading dose: 100 mg | 97.4 percentage of participants |
| Tigecycline | Percentage of Participants Per Tigecycline Loading Dose and Maintenance Dose | Loading dose: Other | 2.6 percentage of participants |
| Tigecycline | Percentage of Participants Per Tigecycline Loading Dose and Maintenance Dose | Maintenance dose: 50 mg twice a day | 93.6 percentage of participants |
| Tigecycline | Percentage of Participants Per Tigecycline Loading Dose and Maintenance Dose | Maintenance dose: 50 mg twice a day + Other | 0.6 percentage of participants |
Secondary
Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Direct Examination
Microbiological sampling results categorized according to direct examination (identification of the class of germs).
Time frame: Post-baseline (Day 1) through last dose of study treatment or up to 25 months
Population: ITT population. N=number of participants with analyzable data at observation; participants may be represented in \>1 category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Direct Examination | Gram negative bacilli | 66.7 percentage of participants |
| Tigecycline | Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Direct Examination | Gram positive cocci | 27.3 percentage of participants |
| Tigecycline | Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Direct Examination | Polymicrobial | 18.2 percentage of participants |
| Tigecycline | Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Direct Examination | Gram positive bacilli | 3.0 percentage of participants |
Secondary
Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Positive Blood Culture
Microbiological sampling results categorized as a positive blood culture (presence of infection).
Time frame: Post-baseline (Day 1) through last dose of study treatment or up to 25 months
Population: ITT population. N=number of participants with analyzable data at observation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tigecycline | Percentage of Participants With Microbiological Sampling Results During Treatment Phase With Tigecycline: Positive Blood Culture | 8.8 percentage of participants |