Trial Outcomes & Findings for Ceftobiprole in the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infections (NCT NCT03137173)
NCT ID: NCT03137173
Last Updated: 2023-05-12
Results Overview
Comparison of early clinical response, including ≥ 20% reduction from baseline in the primary lesion area (based on ruler measurements), survival for ≥ 72 hours and no rescue therapy in the ITT population
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
679 participants
Primary outcome timeframe
48-72 hours after start of study drug treatment
Results posted on
2023-05-12
Participant Flow
Patients with an ABSSSI who received any systemic antibacterial treatment within 14 days, or topical antibacterial administration on the primary lesion within 96 hours, before first infusion of study drug were not allowed to enter the study. Hospitalization in a medical clinic was mandatory for the first 72 hours.
3 randomized patients were not dosed, due to ICF withdrawal (2 patients) and death (1 patient).
Participant milestones
| Measure |
Ceftobiprole Medocaril
Patients treated with ceftobiprole medocaril 500 mg every 8 hours (with dose adjustment for renal impairment).
|
Vancomycin+Aztreonam
Patients treated with vancomycin 1000 mg (or 15 mg/kg) every 12 hours plus aztreonam 1000 mg every 12 hours (both with dose adjustment for renal impairment). Vancomycin dose adjustment for obese and hypermetabolic patients was according to local standard of care. The requirement for aztreonam therapy was to be reassessed at the 72-hour study visit.
|
|---|---|---|
|
Overall Study
STARTED
|
335
|
344
|
|
Overall Study
COMPLETED
|
309
|
308
|
|
Overall Study
NOT COMPLETED
|
26
|
36
|
Reasons for withdrawal
| Measure |
Ceftobiprole Medocaril
Patients treated with ceftobiprole medocaril 500 mg every 8 hours (with dose adjustment for renal impairment).
|
Vancomycin+Aztreonam
Patients treated with vancomycin 1000 mg (or 15 mg/kg) every 12 hours plus aztreonam 1000 mg every 12 hours (both with dose adjustment for renal impairment). Vancomycin dose adjustment for obese and hypermetabolic patients was according to local standard of care. The requirement for aztreonam therapy was to be reassessed at the 72-hour study visit.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
8
|
13
|
|
Overall Study
Death
|
1
|
3
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
13
|
18
|
|
Overall Study
Other reasons
|
3
|
2
|
Baseline Characteristics
Ceftobiprole in the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infections
Baseline characteristics by cohort
| Measure |
Ceftobiprole Medocaril
n=335 Participants
Patients treated with ceftobiprole medocaril 500 mg every 8 hours (with dose adjustment for renal impairment). Duration of infusion: 2 hours.
|
Vancomycin+Aztreonam
n=344 Participants
Vancomycin 1000 mg (or 15 mg/kg) every 12 hours plus aztreonam 1000 mg every 12 hours (both with dose adjustment for renal impairment). Vancomycin dose adjustment for obese and hypermetabolic patients was according to local standard of care. The requirement for aztreonam therapy was to be reassessed at the 72-hour study visit. Duration of vancomycin infusion: 2 hours; duration of aztreonam infusion: 0.5 hours.
|
Total
n=679 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
294 Participants
n=39 Participants
|
292 Participants
n=41 Participants
|
586 Participants
n=35 Participants
|
|
Age, Categorical
>=65 years
|
41 Participants
n=39 Participants
|
52 Participants
n=41 Participants
|
93 Participants
n=35 Participants
|
|
Sex: Female, Male
Female
|
137 Participants
n=39 Participants
|
143 Participants
n=41 Participants
|
280 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
198 Participants
n=39 Participants
|
201 Participants
n=41 Participants
|
399 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
White
|
318 Participants
n=39 Participants
|
330 Participants
n=41 Participants
|
648 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
7 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
15 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
4 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
7 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Other
|
5 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
7 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
103 Participants
n=39 Participants
|
115 Participants
n=41 Participants
|
218 Participants
n=35 Participants
|
|
Region of Enrollment
Hungary
|
2 participants
n=39 Participants
|
1 participants
n=41 Participants
|
3 participants
n=35 Participants
|
|
Region of Enrollment
United States
|
203 participants
n=39 Participants
|
215 participants
n=41 Participants
|
418 participants
n=35 Participants
|
|
Region of Enrollment
Ukraine
|
82 participants
n=39 Participants
|
80 participants
n=41 Participants
|
162 participants
n=35 Participants
|
|
Region of Enrollment
Bulgaria
|
48 participants
n=39 Participants
|
48 participants
n=41 Participants
|
96 participants
n=35 Participants
|
|
Type of ABSSSI
Cellulitis/erysipelas
|
112 Participants
n=39 Participants
|
111 Participants
n=41 Participants
|
223 Participants
n=35 Participants
|
|
Type of ABSSSI
Major cutaneous abscess
|
96 Participants
n=39 Participants
|
93 Participants
n=41 Participants
|
189 Participants
n=35 Participants
|
|
Type of ABSSSI
Wound infection
|
127 Participants
n=39 Participants
|
140 Participants
n=41 Participants
|
267 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: 48-72 hours after start of study drug treatmentPopulation: ITT population
Comparison of early clinical response, including ≥ 20% reduction from baseline in the primary lesion area (based on ruler measurements), survival for ≥ 72 hours and no rescue therapy in the ITT population
Outcome measures
| Measure |
Ceftobiprole Medocaril
n=335 Participants
Patients treated with ceftobiprole medocaril 500 mg every 8 hours (with dose adjustment for renal impairment). Duration of infusion: 2 hours.
|
Vancomycin+Aztreonam
n=344 Participants
Vancomycin 1000 mg (or 15 mg/kg) every 12 hours plus aztreonam 1000 mg every 12 hours (both with dose adjustment for renal impairment). Vancomycin dose adjustment for obese and hypermetabolic patients was according to local standard of care. The requirement for aztreonam therapy was to be reassessed at the 72-hour study visit. Duration of vancomycin infusion: 2 hours; duration of aztreonam infusion: 0.5 hours.
|
|---|---|---|
|
Early Clinical Response
|
306 Participants
|
303 Participants
|
SECONDARY outcome
Timeframe: 15-22 days after randomizationPopulation: ITT population
Comparison of investigator-assessed clinical success (based on resolution of baseline signs and symptoms of the primary infection) in the ITT population
Outcome measures
| Measure |
Ceftobiprole Medocaril
n=335 Participants
Patients treated with ceftobiprole medocaril 500 mg every 8 hours (with dose adjustment for renal impairment). Duration of infusion: 2 hours.
|
Vancomycin+Aztreonam
n=344 Participants
Vancomycin 1000 mg (or 15 mg/kg) every 12 hours plus aztreonam 1000 mg every 12 hours (both with dose adjustment for renal impairment). Vancomycin dose adjustment for obese and hypermetabolic patients was according to local standard of care. The requirement for aztreonam therapy was to be reassessed at the 72-hour study visit. Duration of vancomycin infusion: 2 hours; duration of aztreonam infusion: 0.5 hours.
|
|---|---|---|
|
Investigator-assessed Clinical Success in the ITT Population
|
302 Participants
|
306 Participants
|
SECONDARY outcome
Timeframe: 15-22 days after randomizationPopulation: CE population
Comparison of investigator-assessed clinical success (based on resolution of baseline signs and symptoms of the primary infection) in the clinically evaluable (CE) population
Outcome measures
| Measure |
Ceftobiprole Medocaril
n=283 Participants
Patients treated with ceftobiprole medocaril 500 mg every 8 hours (with dose adjustment for renal impairment). Duration of infusion: 2 hours.
|
Vancomycin+Aztreonam
n=293 Participants
Vancomycin 1000 mg (or 15 mg/kg) every 12 hours plus aztreonam 1000 mg every 12 hours (both with dose adjustment for renal impairment). Vancomycin dose adjustment for obese and hypermetabolic patients was according to local standard of care. The requirement for aztreonam therapy was to be reassessed at the 72-hour study visit. Duration of vancomycin infusion: 2 hours; duration of aztreonam infusion: 0.5 hours.
|
|---|---|---|
|
Investigator-assessed Clinical Success in the Clinically Evaluable (CE) Population
|
277 Participants
|
279 Participants
|
Adverse Events
Ceftobiprole Medocaril
Serious events: 6 serious events
Other events: 63 other events
Deaths: 1 deaths
Vancomycin+Aztreonam
Serious events: 12 serious events
Other events: 47 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Ceftobiprole Medocaril
n=334 participants at risk
Patients treated with ceftobiprole medocaril 500 mg every 8 hours (with dose adjustment for renal impairment).
Ceftobiprole medocaril: A reconstituted solution of 500 mg of ceftobiprole in 250 mL of water for injection was administered IV every 8 hours (with dose adjustment for renal impairment) for a minimum of 5 days and a maximum of 10 days. Treatment could be extended up to 14 days if in the investigator's opinion this was required, and the extension was approved by the sponsor's medical monitor. Duration of each infusion: 2 hours.
|
Vancomycin+Aztreonam
n=342 participants at risk
Patients treated with vancomycin 1000 mg (or 15 mg/kg) every 12 hours plus aztreonam 1000 mg every 12 hours (both with dose adjustment for renal impairment).
Vancomycin+aztreonam: vancomycin 1000 mg (or 15 mg/kg) every 12 hours (with dose adjustment for renal impairment). Vancomycin dose adjustment for obese and hypermetabolic patients was according to local standard of care. Duration of infusion: 2 hours.
Aztreonam for Injection for IV infusion must have been reconstituted with at least 3 mL sterile water for injection. The reconstituted solution of aztreonam must have been further diluted with 100 mL NaCl 0.9% solution for injection, resulting in an aztreonam concentration of 10 mg/mL (1%). Aztreonam 1000 mg was to be administered as a 0.5-hour IV infusion every 12 hours. If CLCR was \< 30 mL/min (i.e., severe renal impairment), the aztreonam dosage regimen might have been adjusted. The requirement for aztreonam therapy was to be reassessed at the 72-hour study visit.
|
|---|---|---|
|
Cardiac disorders
CARDIAC ARREST
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
General disorders
MULTIPLE ORGAN DYSFUNCTION SYNDROME
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Immune system disorders
MULTIPLE ALLERGIES
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Infections and infestations
SKIN BACTERIAL INFECTION
|
0.30%
1/334 • Up to 35 days after last treatment
|
0.88%
3/342 • Up to 35 days after last treatment
|
|
Infections and infestations
CELLULITIS
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.58%
2/342 • Up to 35 days after last treatment
|
|
Infections and infestations
NECROTISING FASCIITIS
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Infections and infestations
PNEUMONIA
|
0.30%
1/334 • Up to 35 days after last treatment
|
0.00%
0/342 • Up to 35 days after last treatment
|
|
Infections and infestations
SEPSIS
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Infections and infestations
SEPTIC SHOCK
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE
|
0.30%
1/334 • Up to 35 days after last treatment
|
0.00%
0/342 • Up to 35 days after last treatment
|
|
Musculoskeletal and connective tissue disorders
RHABDOMYOLYSIS
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHIAL OBSTRUCTION
|
0.30%
1/334 • Up to 35 days after last treatment
|
0.00%
0/342 • Up to 35 days after last treatment
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Skin and subcutaneous tissue disorders
ANGIOEDEMA
|
0.00%
0/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
0.30%
1/334 • Up to 35 days after last treatment
|
0.00%
0/342 • Up to 35 days after last treatment
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.30%
1/334 • Up to 35 days after last treatment
|
0.00%
0/342 • Up to 35 days after last treatment
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
0.30%
1/334 • Up to 35 days after last treatment
|
0.29%
1/342 • Up to 35 days after last treatment
|
Other adverse events
| Measure |
Ceftobiprole Medocaril
n=334 participants at risk
Patients treated with ceftobiprole medocaril 500 mg every 8 hours (with dose adjustment for renal impairment).
Ceftobiprole medocaril: A reconstituted solution of 500 mg of ceftobiprole in 250 mL of water for injection was administered IV every 8 hours (with dose adjustment for renal impairment) for a minimum of 5 days and a maximum of 10 days. Treatment could be extended up to 14 days if in the investigator's opinion this was required, and the extension was approved by the sponsor's medical monitor. Duration of each infusion: 2 hours.
|
Vancomycin+Aztreonam
n=342 participants at risk
Patients treated with vancomycin 1000 mg (or 15 mg/kg) every 12 hours plus aztreonam 1000 mg every 12 hours (both with dose adjustment for renal impairment).
Vancomycin+aztreonam: vancomycin 1000 mg (or 15 mg/kg) every 12 hours (with dose adjustment for renal impairment). Vancomycin dose adjustment for obese and hypermetabolic patients was according to local standard of care. Duration of infusion: 2 hours.
Aztreonam for Injection for IV infusion must have been reconstituted with at least 3 mL sterile water for injection. The reconstituted solution of aztreonam must have been further diluted with 100 mL NaCl 0.9% solution for injection, resulting in an aztreonam concentration of 10 mg/mL (1%). Aztreonam 1000 mg was to be administered as a 0.5-hour IV infusion every 12 hours. If CLCR was \< 30 mL/min (i.e., severe renal impairment), the aztreonam dosage regimen might have been adjusted. The requirement for aztreonam therapy was to be reassessed at the 72-hour study visit.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
10.8%
36/334 • Up to 35 days after last treatment
|
5.8%
20/342 • Up to 35 days after last treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
6.3%
21/334 • Up to 35 days after last treatment
|
4.7%
16/342 • Up to 35 days after last treatment
|
|
Nervous system disorders
Headache
|
5.7%
19/334 • Up to 35 days after last treatment
|
7.0%
24/342 • Up to 35 days after last treatment
|
Additional Information
Project Physician
Basilea Pharmaceutica International Ltd.
Phone: +41 79 701 0551
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60