Trial Outcomes & Findings for Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem in Complicated Intraabdominal Infections (NCT NCT01445678)
NCT ID: NCT01445678
Last Updated: 2018-11-16
Results Overview
Clinical cure is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
494 participants
Primary outcome timeframe
TOC; 26-30 days after start of study drug administration
Results posted on
2018-11-16
Participant Flow
Two identical P3 protocols were initiated (NCT01445678 and NCT01445665) subsequently, Cubist and FDA agreed that integrated data from the 2 protocols could be analyzed and reported in a single Clinical Study Report. A total of 993 subjects were randomized to both arms, 493 to NCT5678 and 500 to NCT5665. Of these, 485 and 494 received treatment.
Participant milestones
| Measure |
CXA-201 and Metronidazole as Treatment for cIAI
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days.
Of the 979 treated subjects in the integrated analysis set, 482 received CXA.
|
Meropenem as Treatment for cIAI
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days Of the 979 treated subjects in the integrated analysis set, 497 received meropenem.
|
|---|---|---|
|
Overall Study
STARTED
|
482
|
497
|
|
Overall Study
COMPLETED
|
452
|
476
|
|
Overall Study
NOT COMPLETED
|
30
|
21
|
Reasons for withdrawal
| Measure |
CXA-201 and Metronidazole as Treatment for cIAI
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days.
Of the 979 treated subjects in the integrated analysis set, 482 received CXA.
|
Meropenem as Treatment for cIAI
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days Of the 979 treated subjects in the integrated analysis set, 497 received meropenem.
|
|---|---|---|
|
Overall Study
Adverse Event
|
12
|
8
|
|
Overall Study
Lack of Efficacy
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
8
|
5
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
9
|
5
|
Baseline Characteristics
Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem in Complicated Intraabdominal Infections
Baseline characteristics by cohort
| Measure |
CXA-201 and Metronidazole as Treatment for cIAI
n=482 Participants
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
Meropenem as Treatment for cIAI
n=497 Participants
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
Total
n=979 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.6 years
STANDARD_DEVIATION 17.94 • n=99 Participants
|
50.5 years
STANDARD_DEVIATION 16.85 • n=107 Participants
|
50.5 years
STANDARD_DEVIATION 17.38 • n=206 Participants
|
|
Sex: Female, Male
Female
|
206 Participants
n=99 Participants
|
195 Participants
n=107 Participants
|
401 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
276 Participants
n=99 Participants
|
302 Participants
n=107 Participants
|
578 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: TOC; 26-30 days after start of study drug administrationPopulation: MITT: Randomized patients, with baseline pathogen.
Clinical cure is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.
Outcome measures
| Measure |
Meropenem as Treatment for cIAI
n=417 Participants
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
CXA-201 and Metronidazole as Treatment for cIAI
n=389 Participants
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
|---|---|---|
|
The Percentage of Subjects With Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population
|
87.3 percentage of subjects
|
83.0 percentage of subjects
|
SECONDARY outcome
Timeframe: TOC; 26-30 days after start of study drug administrationPopulation: Microbiologically evaluable: Treated patients, complied with protocol, with pathogens susceptible to study drug.
Success is eradication (absence of the baseline pathogen in a specimen appropriately obtained from the original site of infection) or presumed eradication (absence of material to culture in a subject who was assessed as a clinical cure) for each baseline pathogen
Outcome measures
| Measure |
Meropenem as Treatment for cIAI
n=321 Participants
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
CXA-201 and Metronidazole as Treatment for cIAI
n=275 Participants
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
|---|---|---|
|
The Percentage of Subjects With Microbiological Outcome of Success at the TOC Visit in the Microbiologically Evaluable (ME) Population
|
94.7 percentage of subjects
|
94.2 percentage of subjects
|
SECONDARY outcome
Timeframe: EOT; Within 24 hours of last study drug administrationPopulation: MITT: Microbiological Intent-to-Treat: Randomized patients, with baseline pathogen.
Clinical response is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.
Outcome measures
| Measure |
Meropenem as Treatment for cIAI
n=417 Participants
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
CXA-201 and Metronidazole as Treatment for cIAI
n=389 Participants
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
|---|---|---|
|
The Percentage of Subjects With Clinical Response at End of Therapy (EOT) Visit in the MITT Population
|
92.3 percentage of subjects
|
89.2 percentage of subjects
|
SECONDARY outcome
Timeframe: EOT; Within 24 hours of last study drug administrationPopulation: Microbiologically evaluable: Treated patients, complied with protocol, with pathogens susceptible to study drug.
Clinical response is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.
Outcome measures
| Measure |
Meropenem as Treatment for cIAI
n=321 Participants
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
CXA-201 and Metronidazole as Treatment for cIAI
n=275 Participants
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
|---|---|---|
|
The Percentage of Subjects With Clinical Response at End of Therapy in the ME Population
|
97.5 percentage of subjects
|
97.1 percentage of subjects
|
SECONDARY outcome
Timeframe: LFU; 38 to 45 days after first study drug administrationPopulation: MITT: Randomized patients, with baseline pathogen.
Clinical response is clinical cure at TOC and no signs and symptoms recur or worsen since the TOC visit.
Outcome measures
| Measure |
Meropenem as Treatment for cIAI
n=417 Participants
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
CXA-201 and Metronidazole as Treatment for cIAI
n=389 Participants
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
|---|---|---|
|
The Percentage of Subjects With Clinical Response at Long Term Follow-Up (LFU) in the MITT Population
|
86.6 percentage of subjects
|
82.5 percentage of subjects
|
SECONDARY outcome
Timeframe: LFU; 38 to 45 days after first study drug administrationPopulation: Microbiologically evaluable: Treated patients, complied with protocol, with pathogens susceptible to study drug.
Clinical response is clinical cure at TOC and no signs and symptoms recur or worsen since the TOC visit
Outcome measures
| Measure |
Meropenem as Treatment for cIAI
n=304 Participants
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
CXA-201 and Metronidazole as Treatment for cIAI
n=258 Participants
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
|---|---|---|
|
The Percentage of Subjects With Clinical Response at LFU Visit in the ME Population
|
99.3 percentage of subjects
|
100 percentage of subjects
|
Adverse Events
CXA-201 and Metronidazole as Treatment for cIAI
Serious events: 39 serious events
Other events: 159 other events
Deaths: 0 deaths
Meropenem as Treatment for cIAI
Serious events: 36 serious events
Other events: 138 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
CXA-201 and Metronidazole as Treatment for cIAI
n=482 participants at risk
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
Meropenem as Treatment for cIAI
n=497 participants at risk
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
|---|---|---|
|
Infections and infestations
Septic shock
|
0.62%
3/482
|
0.40%
2/497
|
|
Infections and infestations
Abdominal abscess
|
0.41%
2/482
|
0.40%
2/497
|
|
Infections and infestations
Pelvic abscess
|
0.21%
1/482
|
0.40%
2/497
|
|
Infections and infestations
Clostridium difficile colitis
|
0.21%
1/482
|
0.20%
1/497
|
|
Infections and infestations
Adominal infection
|
0.21%
1/482
|
0.00%
0/497
|
|
Infections and infestations
Infectious peritonitis
|
0.21%
1/482
|
0.00%
0/497
|
|
Infections and infestations
Lung infection pseudomonal
|
0.21%
1/482
|
0.00%
0/497
|
|
Infections and infestations
Peridiverticular abscess
|
0.21%
1/482
|
0.00%
0/497
|
|
Infections and infestations
Pneumonia staphylococcal
|
0.21%
1/482
|
0.00%
0/497
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.21%
1/482
|
0.00%
0/497
|
|
Infections and infestations
Urinary tract infection
|
0.21%
1/482
|
0.00%
0/497
|
|
Infections and infestations
Liver abscess
|
0.00%
0/482
|
0.60%
3/497
|
|
Infections and infestations
Pneumonia
|
0.00%
0/482
|
0.40%
2/497
|
|
Infections and infestations
Subdiaphragmatic abscess
|
0.00%
0/482
|
0.40%
2/497
|
|
Infections and infestations
Appendiceal abscess
|
0.00%
0/482
|
0.20%
1/497
|
|
Infections and infestations
Device related infection
|
0.00%
0/482
|
0.20%
1/497
|
|
Infections and infestations
Gallbladder abscess
|
0.00%
0/482
|
0.20%
1/497
|
|
Infections and infestations
Graft infection
|
0.00%
0/482
|
0.20%
1/497
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/482
|
0.20%
1/497
|
|
Infections and infestations
Pseudomembranous colitis
|
0.00%
0/482
|
0.20%
1/497
|
|
Infections and infestations
Sepsis
|
0.00%
0/482
|
0.20%
1/497
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.21%
1/482
|
0.40%
2/497
|
|
Gastrointestinal disorders
Ileus
|
0.21%
1/482
|
0.20%
1/497
|
|
Gastrointestinal disorders
Nausea
|
0.21%
1/482
|
0.20%
1/497
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Enterocutaneous fistula
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Rectal perforation
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.21%
1/482
|
0.00%
0/497
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/482
|
0.20%
1/497
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.21%
1/482
|
0.40%
2/497
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.21%
1/482
|
0.20%
1/497
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.21%
1/482
|
0.20%
1/497
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.21%
1/482
|
0.00%
0/497
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.21%
1/482
|
0.00%
0/497
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/482
|
0.20%
1/497
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/482
|
0.20%
1/497
|
|
Injury, poisoning and procedural complications
Wound evisceration
|
0.41%
2/482
|
0.00%
0/497
|
|
Injury, poisoning and procedural complications
Anastomotic leak
|
0.21%
1/482
|
0.20%
1/497
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.21%
1/482
|
0.20%
1/497
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
0.21%
1/482
|
0.00%
0/497
|
|
Injury, poisoning and procedural complications
Suture rupture
|
0.21%
1/482
|
0.00%
0/497
|
|
Injury, poisoning and procedural complications
Abdominal wound dehiscence
|
0.00%
0/482
|
0.20%
1/497
|
|
Injury, poisoning and procedural complications
Pneumoconiosis
|
0.00%
0/482
|
0.20%
1/497
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/482
|
0.20%
1/497
|
|
General disorders
Multi-organ failure
|
0.62%
3/482
|
0.00%
0/497
|
|
General disorders
Sudden death
|
0.41%
2/482
|
0.00%
0/497
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/482
|
0.20%
1/497
|
|
Cardiac disorders
Cardiac failure
|
0.21%
1/482
|
0.20%
1/497
|
|
Cardiac disorders
Myocardial infarction
|
0.21%
1/482
|
0.20%
1/497
|
|
Cardiac disorders
Cardiogenic shock
|
0.21%
1/482
|
0.00%
0/497
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.21%
1/482
|
0.00%
0/497
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/482
|
0.20%
1/497
|
|
Cardiac disorders
Cardiovascular insufficiency
|
0.00%
0/482
|
0.20%
1/497
|
|
Vascular disorders
Deep vein thrombosis
|
0.21%
1/482
|
0.00%
0/497
|
|
Vascular disorders
Pelvic venous thrombosis
|
0.21%
1/482
|
0.00%
0/497
|
|
Vascular disorders
Shock haemorrhagic
|
0.21%
1/482
|
0.00%
0/497
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/482
|
0.20%
1/497
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
0.00%
0/482
|
0.20%
1/497
|
|
Nervous system disorders
Ischaemic stroke
|
0.41%
2/482
|
0.00%
0/497
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/482
|
0.20%
1/497
|
|
Nervous system disorders
Transient ischaemic attach
|
0.00%
0/482
|
0.20%
1/497
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.21%
1/482
|
0.00%
0/497
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/482
|
0.40%
2/497
|
|
Hepatobiliary disorders
Bilary fistula
|
0.00%
0/482
|
0.20%
1/497
|
|
Hepatobiliary disorders
Perforation bile duct
|
0.00%
0/482
|
0.20%
1/497
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.21%
1/482
|
0.00%
0/497
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/482
|
0.20%
1/497
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
0.21%
1/482
|
0.00%
0/497
|
|
Investigations
Hepatic enzyme increased
|
0.21%
1/482
|
0.00%
0/497
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.21%
1/482
|
0.00%
0/497
|
|
Renal and urinary disorders
Renal failure
|
0.21%
1/482
|
0.00%
0/497
|
|
Reproductive system and breast disorders
Atrophic vulvovaginitis
|
0.21%
1/482
|
0.00%
0/497
|
|
Endocrine disorders
Goitre
|
0.00%
0/482
|
0.20%
1/497
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/482
|
0.20%
1/497
|
Other adverse events
| Measure |
CXA-201 and Metronidazole as Treatment for cIAI
n=482 participants at risk
CXA-201 and metronidazole: CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
|
Meropenem as Treatment for cIAI
n=497 participants at risk
Meropenem: Meropenem IV infusion (1000mg q8h) for 4-14 days
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.2%
6/482
|
0.80%
4/497
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
1.7%
8/482
|
1.0%
5/497
|
|
Cardiac disorders
Atrial fibrillation
|
1.2%
6/482
|
0.40%
2/497
|
|
Cardiac disorders
Tachycardia
|
1.5%
7/482
|
1.8%
9/497
|
|
Gastrointestinal disorders
Abdominal pain
|
1.2%
6/482
|
0.40%
2/497
|
|
Gastrointestinal disorders
Constipation
|
1.9%
9/482
|
1.2%
6/497
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
30/482
|
5.0%
25/497
|
|
Gastrointestinal disorders
Dyspepsia
|
0.41%
2/482
|
1.4%
7/497
|
|
Gastrointestinal disorders
Nausea
|
7.7%
37/482
|
5.6%
28/497
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
16/482
|
3.8%
19/497
|
|
General disorders
Oedema peripheral
|
1.9%
9/482
|
0.80%
4/497
|
|
General disorders
Pyrexia
|
5.2%
25/482
|
4.0%
20/497
|
|
Infections and infestations
Pneumonia
|
1.0%
5/482
|
0.80%
4/497
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
1.9%
9/482
|
1.6%
8/497
|
|
Injury, poisoning and procedural complications
Seroma
|
1.2%
6/482
|
1.4%
7/497
|
|
Investigations
Alanine aminotransferase increased
|
1.5%
7/482
|
1.0%
5/497
|
|
Investigations
Aspartate aminotransferase increased
|
1.0%
5/482
|
0.60%
3/497
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.62%
3/482
|
1.0%
5/497
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.2%
6/482
|
0.60%
3/497
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
1.5%
7/482
|
1.6%
8/497
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.83%
4/482
|
1.8%
9/497
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.41%
2/482
|
1.0%
5/497
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.9%
14/482
|
1.6%
8/497
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
1.2%
6/482
|
1.0%
5/497
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
1.0%
5/482
|
0.60%
3/497
|
|
Nervous system disorders
Dizziness
|
0.83%
4/482
|
1.0%
5/497
|
|
Nervous system disorders
Headache
|
2.5%
12/482
|
1.8%
9/497
|
|
Psychiatric disorders
Anxiety
|
1.9%
9/482
|
1.4%
7/497
|
|
Psychiatric disorders
Insomnia
|
3.5%
17/482
|
2.2%
11/497
|
|
Renal and urinary disorders
Dysuria
|
1.0%
5/482
|
0.40%
2/497
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.21%
1/482
|
1.2%
6/497
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.83%
4/482
|
1.2%
6/497
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.9%
9/482
|
1.4%
7/497
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.83%
4/482
|
1.0%
5/497
|
|
Vascular disorders
Hypertension
|
1.9%
9/482
|
2.0%
10/497
|
|
Vascular disorders
Hypotension
|
1.7%
8/482
|
0.80%
4/497
|
|
Vascular disorders
Phlebitis
|
0.41%
2/482
|
1.0%
5/497
|
Additional Information
Dr. Obi Umeh, Vice President Global Medical Sciences
Cubist Pharmaceuticals, Inc.
Phone: 781-860-8415
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Investigator(s) must undertake not to submit any part of the data from this protocol for publication without the prior consent of Cubist Pharmaceuticals, Inc.
- Publication restrictions are in place
Restriction type: OTHER