Evaluation of the effect of an investigational antibiotic (oritavancin) in the treatment of skin and skin structure infections compared to a commonly used antibiotic.
- Conditions
- Treatment of Patients with acute bacterial skin and skin structure infectionsMedDRA version: 14.0Level: PTClassification code 10065240Term: Wound infection bacterialSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 14.0Level: PTClassification code 10040872Term: Skin infectionSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 14.0Level: PTClassification code 10042343Term: Subcutaneous abscessSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 14.0Level: PTClassification code 10066409Term: Staphylococcal skin infectionSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 14.0Level: PTClassification code 10007882Term: CellulitisSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2010-021424-94-ES
- Lead Sponsor
- The Medicines Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 960
1. Males or females >=18 years old
2. Diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen requiring at least 7 days of IV therapy. A specimen for culture must be obtained whenever possible by an approved protocol method 24 hours before the first dose of study drug. Final culture results are not required prior to initiation of study drug.
3. An ABSSSI which includes one of the following infections:
a. Wound infections: that are either traumatic or surgical in origin defined as an infection characterized by purulent drainage from a wound with surrounding erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, the shortest distance of erythema, oedema, and/or induration extending at least 5 cm from the peripheral margin of the wound), accompanied by signs and systemic inflammation symptoms as listed below. Onset of this infection must have occurred within 7 days prior to randomization and no later than 30 days following the trauma or surgical procedure.
b. Cellulitis/erysipelas: a diffuse skin infection characterized by spreading areas of erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, minimum length of 10 cm and width of 7.5 cm), accompanied by signs and systemic inflammation symptoms as listed below. Onset of cellulitis must be within 7 days prior to randomization.
c. Major cutaneous abscess: an infection characterized by a collection of pus within the dermis or deeper that is accompanied by erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, the shortest distance of erythemia, oedema, and/or induration extending at least 5 cm from the peripheral margin of the abscess), accompanied by signs and systemic inflammation symptoms as listed below.
4. ABSSSI must present with at least two of the following signs and symptoms:
a. Purulent drainage or discharge
b. Erythema
c. Fluctuance
d. Heat or localized warmth
e. Oedema/induration
f. Pain or tenderness to palpation
AND At least one of the following signs of systemic inflammation*:
a. Proximal lymph node swelling and tenderness
b. Increased temperature (38.0°C [100.4°F]) (oral route; temperature should not be obtained by rectal, axillary or tympanic routes)
c. Decreased temperature (<36.0°C or [<96.8°F]) (oral route; temperature should not be obtained by rectal, axillary or tympanic routes)
d. Increased WBC (10,000/mm3)
e. Bandemia > 10%
f. C-reactive protein (CRP) > upper limit of normal (ULN)
* If a patient does not have any of the noted signs of systemic inflammation, they may still be enrolled if they meet any of the following conditions:
a. Age >70 years
b. Diabetes mellitus requiring treatment with insulin and/or oral hypoglycaemic medications
c. Treatment with immunosuppressive or chemotherapy in the prior 3 months
5. Able to give informed consent and willing to comply with all required study procedures (if necessary informed consent may be obtained from the patient?s legal representative, with a witness present).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 815
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 145
;
1. Males or females >=18 years old
2. Diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen requiring at least 7 days of IV therapy. A specimen for culture must be obtained whenever possible by an approved protocol method 24 hours before the first dose of study drug. Final culture results are not required prior to initiation of study drug.
3. An ABSSSI which includes one of the following infections:
a. Wound infections: that are either traumatic or surgical in origin defined as an infection characterized by purulent drainage from a wound with surrounding erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, the shortest distance of erythema, oedema, and/or induration extending at least 5 cm from the peripheral margin of the wound), accompanied by signs and systemic inflammation symptoms as listed below. Onset of this infection must have occurred within 7 days prior to randomization and no later than 30 days following the trauma or surgical procedure.
b. Cellulitis/erysipelas: a diffuse skin infection characterized by spreading areas of erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, minimum length of 10 cm and width of 7.5 cm), accompanied by signs and systemic inflammation symptoms as listed below. Onset of cellulitis must be within 7 days prior to randomization.
c. Major cutaneous abscess: an infection characterized by a collection of pus within the dermis or deeper that is accompanied by erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, the shortest distance of erythemia, oedema, and/or induration extending at least 5 cm from the peripheral margin of the abscess), accompanied by signs and systemic inflammation symptoms as listed below.
4. ABSSSI must present with at least two of the following signs and symptoms:
a. Purulent drainage or discharge
b. Erythema
c. Fluctuance
d. Heat or localized warmth
e. Oedema/induration
f. Pain or tenderness to palpation
AND At least one of the following signs of systemic inflammation*:
a. Proximal lymph node swelling and tenderness
b. Increased temperature (38.0°C [100.4°F]) (oral route; temperature should not be obtained by rectal, axillary or tympanic routes)
c. Decreased temperature (<36.0°C or [<96.8°F]) (oral route; temperature should not be obtained by rectal, axillary or tympanic routes)
d. Increased WBC (10,000/mm3)
e. Bandemia > 10%
f. C-reactive protein (CRP) > upper limit of normal (ULN)
* If a patient does not have any of the noted signs of systemic inflammation, they may still be enrolled if they meet any of the following conditions:
a. Age >70 years
b. Diabetes mellitus requiring treatment with insulin and/or oral hypoglycaemic medications
c. Treatment with immunosuppressive or chemotherapy in the prior 3 months
5. Able to give informed consent and willing to comply with all required study procedures (if necessary informed consent may be obtained from the patient?s legal representative, with a witness present).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 815
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 145
1. Prior systemic or topical antibacterial therapy with activity against suspected or proven Gram-positive pathogens within the preceding 14 days unless:
a. The causative Gram-positive pathogen(s) isolated from the ABSSSI site is resistant in vitro to the antibacterial(s) that was administered with documented clinical progression, or
b. Documented failure to previous ABSSSI antibiotic therapy is available. Documentation of treatment failure must be recorded (eg, record in patient?s medical chart of wound size prior to initial treatment with demonstration of progression on therapy, discussion with prior treating physician, consultation of patient?s medical records, and/or consultation of available documentation of treatment (eg, prescription) before study randomization,
c. Patient received a single dose of a short-acting antibacterial therapy (eg, surgical prophylaxis) three or more days before randomization (ie, patients cannot have received any antibiotic treatment within 72 hours of randomization).
2. Infections associated with, or in close proximity to, a prosthetic device
3. Severe sepsis or refractory shock
4. Known or suspected bacteraemia at time of screening
5. ABSSSI due to or associated with any of the following:
a. Infections suspected or documented to be caused by Gram-negative pathogens (ie, human or animal bites, injuries contaminated with fresh or salt water, external malignant otitis)
b. Wound infections (surgical or traumatic) and abscesses with only Gram-negative pathogens
c. Diabetic foot infections (infection extending distal to the malleoli in a patient with diabetes mellitus and peripheral neuropathy and/or
vascular insufficiency or any ulceration of their foot).
d. Concomitant infection at another site not including a secondary ABSSSI lesion (eg, septic arthritis, endocarditis, osteomyelitis)
e. Infected burns
f. A primary infection secondary to a pre-existing skin disease with associated inflammatory changes such as atopic dermatitis, eczema or hidradenitis suppurativa
g. Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous)
h. Any evolving necrotizing process (ie necrotizing fasciitis), gangrene or infection suspected or proven to be caused by Clostridium species (eg, crepitance on examination of the ABSSSI site and/or surrounding tissue(s) or radiographic evidence of subcutaneous gas in proximity to the infection)
i. Infections known to be caused by a Gram-positive organism with a vancomycin minimum inhibitory concentration (MIC) >2 mcg/mL or clinically failing prior therapy with glycopeptides
j. Catheter site infections
6. Allergy or intolerance to aztreonam or metronidazole in a patient with suspected or proven polymicrobial wound infection involving Gram-negative and/or anaerobic bacteria
7. Currently receiving chronic systemic immunosuppressive therapy such as chemotherapy or prednisone (prednisone at non-immunosuppressive doses of ?15 mg/day is permitted)
8. Last known cluster of differentiation 4 (CD4) count <200 cells/mm3 in patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
9. Neutropenia with absolute neutrophil count (ANC) <500 cells/mm3
10. Significant or life-threatening condition (eg, endocarditis) that would confound or interfere with the assessment of the ABSSSI
11. Women who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 acceptable ;
1. Prior systemic or topical antibacterial therapy with activity against suspected or proven Gram-positive pathogens within the preceding 14 days unless:
a. The causative Gram-positive pathogen(s) isolated from the ABSSSI site is resistant in vitro to the antibacterial(s) that was administered with documented clinical progression, or
b. Documented failure to previous ABSSSI antibiotic therapy is available. Documentation of treatment failure must be recorded (eg, record in patient?s medical chart of wound size prior to initial treatment with demonstration of progression on therapy, discussion with prior treating physician, consultation of patient?s medical records, and/or consultation of available documentation of treatment (eg, prescription) before study randomization,
c. Patient received a single dose of a short-acting antibacterial therapy (eg, surgical prophylaxis) three or more days before randomization (ie, patients cannot have received any antibiotic treatment within 72 hours of randomization).
2. Infections associated with, or in close proximity to, a prosthetic device
3. Severe sepsis or refractory shock
4. Known or suspected bacteraemia at time of screening
5. ABSSSI due to or associated with any of the following:
a. Infections suspected or documented to be caused by Gram-negative pathogens (ie, human or animal bites, injuries contaminated with fresh or salt water, external malignant otitis)
b. Wound infections (surgical or traumatic) and abscesses with only Gram-negative pathogens
c. Diabetic foot infections (infection extending distal to the malleoli in a patient with diabetes mellitus and peripheral neuropathy and/or
vascular insufficiency or any ulceration of their foot).
d. Concomitant infection at another site not including a secondary ABSSSI lesion (eg, septic arthritis, endocarditis, osteomyelitis)
e. Infected burns
f. A primary infection secondary to a pre-existing skin disease with associated inflammatory changes such as atopic dermatitis, eczema or hidradenitis suppurativa
g. Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous)
h. Any evolving necrotizing process (ie necrotizing fasciitis), gangrene or infection suspected or proven to be caused by Clostridium species (eg, crepitance on examination of the ABSSSI site and/or surrounding tissue(s) or radiographic evidence of subcutaneous gas in proximity to the infection)
i. Infections known to be caused by a Gram-positive organism with a vancomycin minimum inhibitory concentration (MIC) >2 mcg/mL or clinically failing prior therapy with glycopeptides
j. Catheter site infections
6. Allergy or intolerance to aztreonam or metronidazole in a patient with suspected or proven polymicrobial wound infection involving Gram-negative and/or anaerobic bacteria
7. Currently receiving chronic systemic immunosuppressive therapy such as chemotherapy or prednisone (prednisone at non-immunosuppressive doses of ?15 mg/day is permitted)
8. Last known cluster of differentiation 4 (CD4) count <200 cells/mm3 in patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
9. Neutropenia with absolute neutrophil count (ANC) <500 cells/mm3
10. Significant or life-threatening condition (eg, endocarditis) that would confound or interfere with the assessment of the ABSSSI
11. Women who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 acceptable
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method