Trial Outcomes & Findings for Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Complicated Intra-abdominal Infections (NCT NCT01844856)

NCT ID: NCT01844856

Last Updated: 2022-01-11

Results Overview

Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection \[cIAI\], unplanned surgical procedures or percutaneous drainage procedures, persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (outcome was neither cure nor failure, or assessment was not available). Participants who were failures at the End-of-Treatment (EOT) visit (within 24 hours of last dose) were considered failures at the TOC visit. The number of participants with a clinical response classification of cure, failure, or indeterminate is presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

541 participants

Primary outcome timeframe

TOC visit: 25-31 days after the first dose of study drug

Results posted on

2022-01-11

Participant Flow

Participant milestones

Participant milestones
Measure
Eravacycline, 1.0 mg/kg q12h
Eravacycline was administered intravenously (IV) at a dose of 1.0 milligrams per kilogram of body weight (mg/kg) every 12 hours (q12h) for a minimum of 4 days and a maximum of 14 days.
Ertapenem, 1.0 g q24h
Ertapenem was administered IV at a dose of 1.0 grams (g) every 24 hours (q24h) for a minimum of 4 days and a maximum of 14 days.
Overall Study
STARTED
270
271
Overall Study
Received at Least 1 Dose of Study Drug
270
268
Overall Study
COMPLETED
246
255
Overall Study
NOT COMPLETED
24
16

Reasons for withdrawal

Reasons for withdrawal
Measure
Eravacycline, 1.0 mg/kg q12h
Eravacycline was administered intravenously (IV) at a dose of 1.0 milligrams per kilogram of body weight (mg/kg) every 12 hours (q12h) for a minimum of 4 days and a maximum of 14 days.
Ertapenem, 1.0 g q24h
Ertapenem was administered IV at a dose of 1.0 grams (g) every 24 hours (q24h) for a minimum of 4 days and a maximum of 14 days.
Overall Study
Lost to Follow-up
15
3
Overall Study
Adverse Event
3
6
Overall Study
Withdrawal by Subject
3
2
Overall Study
Noncompliance
2
3
Overall Study
Enterococcus Resistant
0
1
Overall Study
Inadvertently Not Scheduled
1
0
Overall Study
Randomized but was a Screen Failure
0
1

Baseline Characteristics

Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Complicated Intra-abdominal Infections

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Eravacycline, 1.0 mg/kg q12h
n=270 Participants
Eravacycline was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days.
Ertapenem, 1.0 g q24h
n=271 Participants
Ertapenem was administered IV at a dose of 1.0 g q24h for a minimum of 4 days and a maximum of 14 days.
Total
n=541 Participants
Total of all reporting groups
Age, Continuous
54.8 years
STANDARD_DEVIATION 16.92 • n=5 Participants
54.8 years
STANDARD_DEVIATION 16.09 • n=7 Participants
54.8 years
STANDARD_DEVIATION 16.49 • n=5 Participants
Sex: Female, Male
Female
114 Participants
n=5 Participants
108 Participants
n=7 Participants
222 Participants
n=5 Participants
Sex: Female, Male
Male
156 Participants
n=5 Participants
163 Participants
n=7 Participants
319 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
8 Participants
n=5 Participants
9 Participants
n=7 Participants
17 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
261 Participants
n=5 Participants
262 Participants
n=7 Participants
523 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
White
263 participants
n=5 Participants
260 participants
n=7 Participants
523 participants
n=5 Participants
Race/Ethnicity, Customized
Black or African American
1 participants
n=5 Participants
3 participants
n=7 Participants
4 participants
n=5 Participants
Race/Ethnicity, Customized
Asian
1 participants
n=5 Participants
3 participants
n=7 Participants
4 participants
n=5 Participants
Race/Ethnicity, Customized
Other Race
4 participants
n=5 Participants
5 participants
n=7 Participants
9 participants
n=5 Participants
Race/Ethnicity, Customized
Unknown or Not Reported
1 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
Region of Enrollment
Russian Federation
28 participants
n=5 Participants
24 participants
n=7 Participants
52 participants
n=5 Participants
Region of Enrollment
Romania
42 participants
n=5 Participants
42 participants
n=7 Participants
84 participants
n=5 Participants
Region of Enrollment
United States
18 participants
n=5 Participants
20 participants
n=7 Participants
38 participants
n=5 Participants
Region of Enrollment
Ukraine
38 participants
n=5 Participants
38 participants
n=7 Participants
76 participants
n=5 Participants
Region of Enrollment
Czech Republic
14 participants
n=5 Participants
17 participants
n=7 Participants
31 participants
n=5 Participants
Region of Enrollment
Latvia
25 participants
n=5 Participants
23 participants
n=7 Participants
48 participants
n=5 Participants
Region of Enrollment
South Africa
0 participants
n=5 Participants
1 participants
n=7 Participants
1 participants
n=5 Participants
Region of Enrollment
Bulgaria
45 participants
n=5 Participants
44 participants
n=7 Participants
89 participants
n=5 Participants
Region of Enrollment
Lithuania
26 participants
n=5 Participants
26 participants
n=7 Participants
52 participants
n=5 Participants
Region of Enrollment
Germany
2 participants
n=5 Participants
2 participants
n=7 Participants
4 participants
n=5 Participants
Region of Enrollment
Estonia
32 participants
n=5 Participants
34 participants
n=7 Participants
66 participants
n=5 Participants

PRIMARY outcome

Timeframe: TOC visit: 25-31 days after the first dose of study drug

Population: All randomized participants who had baseline bacterial pathogens that cause cIAI and against at least one of which the investigational drug has in vitro antibacterial activity (micro-ITT population).

Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection \[cIAI\], unplanned surgical procedures or percutaneous drainage procedures, persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (outcome was neither cure nor failure, or assessment was not available). Participants who were failures at the End-of-Treatment (EOT) visit (within 24 hours of last dose) were considered failures at the TOC visit. The number of participants with a clinical response classification of cure, failure, or indeterminate is presented.

Outcome measures

Outcome measures
Measure
Eravacycline, 1.0 mg/kg q12h
n=220 Participants
Eravacycline was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days.
Ertapenem, 1.0 g q24h
n=226 Participants
Ertapenem was administered IV at a dose of 1.0 g q24h for a minimum of 4 days and a maximum of 14 days.
Clinical Response of Eravacycline and Ertapenem Treatment Arms at the Test-of-cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population
Failure
19 participants
11 participants
Clinical Response of Eravacycline and Ertapenem Treatment Arms at the Test-of-cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population
Indeterminate
10 participants
17 participants
Clinical Response of Eravacycline and Ertapenem Treatment Arms at the Test-of-cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population
Cure
191 participants
198 participants

SECONDARY outcome

Timeframe: TOC visit: 25-31 days after first dose

Population: All randomized participants who received at least 1 dose of study drug (MITT population).

Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection \[cIAI\], unplanned surgical procedures or percutaneous drainage procedures, persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (outcome was neither cure nor failure, or assessment was not available). Participants who were failures at the EOT visit (within 24 hours of last dose) were considered failures at the TOC visit. The number of participants with a clinical response classification of cure, failure, or indeterminate is presented.

Outcome measures

Outcome measures
Measure
Eravacycline, 1.0 mg/kg q12h
n=270 Participants
Eravacycline was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days.
Ertapenem, 1.0 g q24h
n=268 Participants
Ertapenem was administered IV at a dose of 1.0 g q24h for a minimum of 4 days and a maximum of 14 days.
Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Modified Intent-to-treat (MITT) Population at the TOC Visit
Cure
235 participants
238 participants
Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Modified Intent-to-treat (MITT) Population at the TOC Visit
Failure
19 participants
15 participants
Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Modified Intent-to-treat (MITT) Population at the TOC Visit
Indeterminate
16 participants
15 participants

SECONDARY outcome

Timeframe: TOC visit: 25-31 days after first dose

Population: All randomized participants who had no major protocol deviations (CE population).

Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection \[cIAI\], unplanned surgical procedures or percutaneous drainage procedures, persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (outcome was neither cure nor failure, or assessment was not available). Participants who were failures at the EOT visit (within 24 hours of last dose) were considered failures at the TOC visit. The number of participants with a clinical response classification of cure, failure, or indeterminate is presented.

Outcome measures

Outcome measures
Measure
Eravacycline, 1.0 mg/kg q12h
n=239 Participants
Eravacycline was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days.
Ertapenem, 1.0 g q24h
n=238 Participants
Ertapenem was administered IV at a dose of 1.0 g q24h for a minimum of 4 days and a maximum of 14 days.
Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Clinically Evaluable (CE) Population at the TOC Visit
Cure
222 participants
225 participants
Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Clinically Evaluable (CE) Population at the TOC Visit
Failure
17 participants
13 participants
Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Clinically Evaluable (CE) Population at the TOC Visit
Indeterminate
0 participants
0 participants

Adverse Events

Eravacycline, 1.0 mg/kg q12h

Serious events: 17 serious events
Other events: 43 other events
Deaths: 0 deaths

Ertapenem, 1.0 g q24h

Serious events: 16 serious events
Other events: 28 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Eravacycline, 1.0 mg/kg q12h
n=270 participants at risk
Eravacycline was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days.
Ertapenem, 1.0 g q24h
n=268 participants at risk
Ertapenem was administered IV at a dose of 1.0 g q24h for a minimum of 4 days and a maximum of 14 days.
Cardiac disorders
Atrial fibrillation
0.00%
0/270
0.37%
1/268
Cardiac disorders
Cardiopulmonary failure
0.00%
0/270
0.37%
1/268
Cardiac disorders
Pulseless electrical activity
0.00%
0/270
0.37%
1/268
Cardiac disorders
Supraventricular tachycardia
0.00%
0/270
0.37%
1/268
Gastrointestinal disorders
Abdominal compartment syndrome
0.00%
0/270
0.37%
1/268
Gastrointestinal disorders
Colonic fistula
0.00%
0/270
0.37%
1/268
Gastrointestinal disorders
Diverticular perforation
0.37%
1/270
0.00%
0/268
Gastrointestinal disorders
Duodenal ulcer haemorrhage
0.37%
1/270
0.37%
1/268
Gastrointestinal disorders
Ileus
0.37%
1/270
0.00%
0/268
Gastrointestinal disorders
Intestinal fistula
0.37%
1/270
0.00%
0/268
Gastrointestinal disorders
Oesophageal fistula
0.37%
1/270
0.00%
0/268
Gastrointestinal disorders
Pancreatitis necrotising
0.37%
1/270
0.00%
0/268
General disorders
Multi-organ failure
0.37%
1/270
0.00%
0/268
Infections and infestations
Abdominal abscess
0.37%
1/270
0.75%
2/268
Infections and infestations
Empyema
0.37%
1/270
0.00%
0/268
Infections and infestations
Haematoma infection
0.37%
1/270
0.00%
0/268
Infections and infestations
Liver abscess
0.37%
1/270
0.37%
1/268
Infections and infestations
Peritoneal abscess
0.00%
0/270
0.37%
1/268
Infections and infestations
Peritonitis
0.37%
1/270
0.00%
0/268
Infections and infestations
Pneumonia
0.74%
2/270
0.37%
1/268
Infections and infestations
Sepsis
0.00%
0/270
0.37%
1/268
Infections and infestations
Septic shock
0.00%
0/270
0.37%
1/268
Injury, poisoning and procedural complications
Abdominal wound dehiscence
0.37%
1/270
0.00%
0/268
Injury, poisoning and procedural complications
Gastrointestinal stoma complication
0.00%
0/270
0.37%
1/268
Injury, poisoning and procedural complications
Splenic rupture
0.37%
1/270
0.00%
0/268
Injury, poisoning and procedural complications
Wound dehiscence
0.74%
2/270
0.37%
1/268
Injury, poisoning and procedural complications
Wound evisceration
0.37%
1/270
0.00%
0/268
Nervous system disorders
Cerebrovascular accident
0.37%
1/270
0.00%
0/268
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
0.00%
0/270
0.37%
1/268
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
0.37%
1/270
0.00%
0/268
Respiratory, thoracic and mediastinal disorders
Pleural effusion
0.37%
1/270
0.00%
0/268
Respiratory, thoracic and mediastinal disorders
Pulmonary artery thrombosis
0.00%
0/270
0.37%
1/268
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.00%
0/270
0.75%
2/268
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
0.00%
0/270
0.37%
1/268
Respiratory, thoracic and mediastinal disorders
Respiratory failure
0.00%
0/270
0.37%
1/268
Surgical and medical procedures
Biliary drainage
0.37%
1/270
0.00%
0/268
Vascular disorders
Deep vein thrombosis
0.37%
1/270
0.00%
0/268

Other adverse events

Other adverse events
Measure
Eravacycline, 1.0 mg/kg q12h
n=270 participants at risk
Eravacycline was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days.
Ertapenem, 1.0 g q24h
n=268 participants at risk
Ertapenem was administered IV at a dose of 1.0 g q24h for a minimum of 4 days and a maximum of 14 days.
Gastrointestinal disorders
Nausea
8.1%
22/270
0.75%
2/268
Gastrointestinal disorders
Vomiting
4.1%
11/270
3.4%
9/268
Blood and lymphatic system disorders
Anaemia
2.6%
7/270
3.4%
9/268
General disorders
Pyrexia
2.2%
6/270
3.0%
8/268
Vascular disorders
Phlebitis
3.0%
8/270
0.37%
1/268

Additional Information

Chief Development Officer

La Jolla Pharmaceutical Company

Phone: +1.617.715.3600

Results disclosure agreements

  • Principal investigator is a sponsor employee At least 60 days prior to submitting or presenting a manuscript, poster, presentation, abstract or other materials relating to the Trial, the PI shall provide to Sponsor all such manuscripts and materials, and Sponsor shall have 60 days to review and comment. If requested, the PI shall remove confidential information prior to submitting or presenting the materials, and shall delay publication or presentation for up to 90 days to allow Sponsor to protect its interests in any such materials.
  • Publication restrictions are in place

Restriction type: OTHER