Trial Outcomes & Findings for Efficacy and Safety Study of Eravacycline Compared With Meropenem in Complicated Intra-abdominal Infections (NCT NCT02784704)

Last Updated: 2022-01-06

Results Overview

Clinical cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no additional antibacterial therapy, surgical, or radiological intervention was required. Clinical failure was defined as death related to complicated intra-abdominal infection (cIAI), persistence of clinical symptoms of cIAI, unplanned surgical or percutaneous drainage procedures for complication or recurrence of cIAI, post-surgical wound infections requiring systemic antibiotics, or initiation of rescue antibacterial drug therapy for treatment of cIAI. Indeterminate/missing was defined as an outcome that was neither a clinical cure nor clinical failure, if the investigator did not complete an assessment, if a study visit was not conducted, or if the subject died for a cause unrelated to cIAI.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

500 participants

Primary outcome timeframe

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

Results posted on

2022-01-06

Participant Flow

Subjects with a diagnosis of complicated intra-abdominal infection (cIAI) requiring surgery were recruited into this study. Subjects were recruited in 65 centers worldwide. The first subject enrolled on 13 October 2016 and the last subject completed on 19 May 2017.

Participant milestones

Participant milestones
Measure	Eravacycline Eravacycline 1.0mg/kg q12h	Meropenem Meropenem 1g q8h
Overall Study STARTED	250	250
Overall Study Treated	250	249
Overall Study COMPLETED	237	241
Overall Study NOT COMPLETED	13	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Eravacycline Eravacycline 1.0mg/kg q12h	Meropenem Meropenem 1g q8h
Overall Study Adverse Event	4	2
Overall Study Lost to Follow-up	6	4
Overall Study Withdrawal by Subject	1	3
Overall Study Subject Non Compliance	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eravacycline n=250 Participants Eravacycline 1.0 mg/kg q12h	Meropenem n=249 Participants Meropenem 1 g q8h	Total n=499 Participants Total of all reporting groups
Age, Categorical >=65 years	70 Participants n=5 Participants	75 Participants n=7 Participants	145 Participants n=5 Participants
Age, Continuous	52.1 years STANDARD_DEVIATION 17.69 • n=5 Participants	52.8 years STANDARD_DEVIATION 18.24 • n=7 Participants	52.4 years STANDARD_DEVIATION 17.931 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	180 Participants n=5 Participants	174 Participants n=7 Participants	354 Participants n=5 Participants
Sex: Female, Male Female	111 Participants n=5 Participants	120 Participants n=7 Participants	231 Participants n=5 Participants
Sex: Female, Male Male	139 Participants n=5 Participants	129 Participants n=7 Participants	268 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	239 Participants n=5 Participants	238 Participants n=7 Participants	477 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	249 Participants n=5 Participants	249 Participants n=7 Participants	498 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Latvia	34 participants n=5 Participants	33 participants n=7 Participants	67 participants n=5 Participants
Region of Enrollment Romania	23 participants n=5 Participants	34 participants n=7 Participants	57 participants n=5 Participants
Region of Enrollment Hungary	10 participants n=5 Participants	20 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Czechia	13 participants n=5 Participants	16 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Ukraine	39 participants n=5 Participants	43 participants n=7 Participants	82 participants n=5 Participants
Region of Enrollment Georgia	8 participants n=5 Participants	16 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment Bulgaria	52 participants n=5 Participants	41 participants n=7 Participants	93 participants n=5 Participants
Region of Enrollment Lithuania	22 participants n=5 Participants	18 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Estonia	20 participants n=5 Participants	11 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment Russia	21 participants n=5 Participants	13 participants n=7 Participants	34 participants n=5 Participants

PRIMARY outcome

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

Population: Microbiological Intent-to-Treat Population: all randomized subjects who have at least one baseline bacterial pathogen that causes cIAI and against which the investigational drug has in vitro antibacterial activity.

Outcome measures

Outcome measures
Measure	Eravacycline n=195 Participants Eravacycline 1.0mg/kg q12h	Meropenem n=205 Participants Meropenem 1g q8h
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population Clinical Failure	7 Participants	7 Participants
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population Indeterminate/missing	11 Participants	11 Participants
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population Clinical Cure	177 Participants	187 Participants

SECONDARY outcome

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

Population: Modified Intent-to-Treat Population: all randomized subjects who receive any amount of study drug.

Outcome measures

Outcome measures
Measure	Eravacycline n=250 Participants Eravacycline 1.0mg/kg q12h	Meropenem n=249 Participants Meropenem 1g q8h
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the All-Treated (MITT) Population Clinical Cure	231 Participants	228 Participants
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the All-Treated (MITT) Population Indeterminate/missing	12 Participants	12 Participants
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the All-Treated (MITT) Population Clinical Failure	7 Participants	9 Participants

SECONDARY outcome

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

Population: Clinically Evaluable: all randomized subjects who meet key inclusion/exclusion criteria and follow other important components of the trial

Outcome measures

Outcome measures
Measure	Eravacycline n=225 Participants Eravacycline 1.0mg/kg q12h	Meropenem n=231 Participants Meropenem 1g q8h
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population Clinical Cure	218 Participants	222 Participants
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population Clinical Failure	7 Participants	9 Participants

Adverse Events

Eravacycline

Serious events: 15 serious events

Other events: 29 other events

Deaths: 4 deaths

Meropenem

Serious events: 16 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Eravacycline n=250 participants at risk Eravacycline 1 mg/kg q12h	Meropenem n=249 participants at risk Meropenem 1 g q8h
Gastrointestinal disorders Nausea	4.8% 12/250 • 52 days All serious adverse events by preferred term, Safety Population	0.80% 2/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Vomiting	3.6% 9/250 • 52 days All serious adverse events by preferred term, Safety Population	2.0% 5/249 • 52 days All serious adverse events by preferred term, Safety Population
General disorders Infusion site phlebitis	3.2% 8/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population

Additional Information

Chief Development Officer

La Jolla Pharmaceutical Company

Phone: 617-715-3600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publications should include input from the PI, his/her colleagues, other PIs in the trial and the Sponsor's personnel; such input should be reflected in the authorship. Agreement of order of authors should be established before writing a manuscript. The PI interested in participating in writing the manuscript should contact the Sponsor. The PI shall not make any publication without the Sponsor's prior written approval, which may be withheld or granted by the Sponsor, in it's sole discretion.
Publication restrictions are in place

Restriction type: OTHER

Measure	Eravacycline n=250 participants at risk Eravacycline 1 mg/kg q12h	Meropenem n=249 participants at risk Meropenem 1 g q8h
Infections and infestations Pneumonia	0.80% 2/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Injury, poisoning and procedural complications Abdominal wound dehiscence	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Metabolism and nutrition disorders Dehydration	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Gastrointestinal inflammation	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Respiratory, thoracic and mediastinal disorders hydrothorax	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Large intestine perforation	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumor	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Melaena	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Pancreatitis acute	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Renal and urinary disorders Ureteric rupture	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Injury, poisoning and procedural complications Wound dehiscence	0.40% 1/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Infections and infestations Abdominal abscess	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.00% 0/249 • 52 days All serious adverse events by preferred term, Safety Population
Cardiac disorders Atrial fibrillation	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Cardiac disorders Cardiac arrest	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Hepatobiliary disorders Cholecystitis acute	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Duodenal ulcer	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Vascular disorders Hypotension	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Ileus	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Gastrointestinal disorders Intestinal fistula	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Cardiac disorders Myocardial infarction	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Blood and lymphatic system disorders Splenic hematoma	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Reproductive system and breast disorders Pelvic fluid collection	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Infections and infestations Peritonitis	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
General disorders Pyrexia	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Renal and urinary disorders Renal failure	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Infections and infestations Sepsis	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Injury, poisoning and procedural complications Suture related complication	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population
Injury, poisoning and procedural complications Wound decomposition	0.00% 0/250 • 52 days All serious adverse events by preferred term, Safety Population	0.40% 1/249 • 52 days All serious adverse events by preferred term, Safety Population