Trial Outcomes & Findings for An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Deep Tissue Infection Due To Candida (NCT NCT00805740)

Last Updated: 2013-08-01

Results Overview

Participants had successful global response if there was clinical response of cure/improvement,microbiological eradication/presumed eradication.Clinical cure:resolution of signs/symptoms (s/s) of Candida infection;no additional systemic/oral antifungal treatment needed.Clinical improvement:significant,but incomplete resolution of s/s of Candida infection;no additional systemic/oral antifungal treatment needed.Microbiological eradication/presumed eradication:baseline pathogen not isolated from original site culture,or culture data not available for participant with successful clinical outcome.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

41 participants

Primary outcome timeframe

End of Treatment (Day 14 to Day 42)

Results posted on

2013-08-01

Participant Flow

Participant milestones

Participant milestones
Measure	Anidulafungin Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Overall Study STARTED	28	13
Overall Study Treated	26	13
Overall Study COMPLETED	17	9
Overall Study NOT COMPLETED	11	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Anidulafungin Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Overall Study Death	7	4
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	1	0
Overall Study Randomized, but not treated	2	0

Baseline Characteristics

An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Deep Tissue Infection Due To Candida

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anidulafungin n=26 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=13 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Total n=39 Participants Total of all reporting groups
Age Continuous	56.3 years STANDARD_DEVIATION 16.2 • n=93 Participants	63.4 years STANDARD_DEVIATION 16.3 • n=4 Participants	58.6 years STANDARD_DEVIATION 16.4 • n=27 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	5 Participants n=4 Participants	14 Participants n=27 Participants
Sex: Female, Male Male	17 Participants n=93 Participants	8 Participants n=4 Participants	25 Participants n=27 Participants

PRIMARY outcome

Timeframe: End of Treatment (Day 14 to Day 42)

Population: Modified Intent-To-Treat (MITT) population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species (sp.).

Outcome measures

Outcome measures
Measure	Anidulafungin n=24 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=13 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Percentage of Participants With Global Response at End of Treatment (Day 14 To Day 42)	83.3 percentage of participants Interval 62.6 to 95.3	61.5 percentage of participants Interval 31.6 to 86.1

SECONDARY outcome

Timeframe: 2-week follow-up (2 weeks after end of treatment [EOT]), 6-week follow-up (6 weeks after EOT)

Population: MITT population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species. Only participants who completed therapy or who had global response of failure at EOT were evaluable for 2- and 6-week follow-up analysis.

Outcome measures

Outcome measures
Measure	Anidulafungin n=21 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=11 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Percentage of Participants With Global Response at 2-week and 6-week Follow-up Visit 6-week follow-up	66.7 percentage of participants Interval 43.0 to 85.4	54.5 percentage of participants Interval 23.4 to 83.3
Percentage of Participants With Global Response at 2-week and 6-week Follow-up Visit 2-week follow-up	76.2 percentage of participants Interval 52.8 to 91.8	54.5 percentage of participants Interval 23.4 to 83.3

SECONDARY outcome

Timeframe: EOT (Day 14 to 42), 2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)

Population: MITT population. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group respectively.

A participant had a successful response if there was clinical response of cure and microbiological success (eradication or presumed eradication). Clinical response of cure: resolution of signs and symptoms attributed to Candida infection; no additional systemic or oral antifungal treatment required to complete the course of therapy. Microbiological eradication or presumed eradication: baseline pathogen not isolated from original site culture, or culture data not available for a participant with successful clinical outcome.

Outcome measures

Outcome measures
Measure	Anidulafungin n=21 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=8 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Percentage of Participants With Response Based on Clinical Cure and Microbiological Success EOT (n=21,8)	81.0 percentage of participants	62.5 percentage of participants
Percentage of Participants With Response Based on Clinical Cure and Microbiological Success 2-week follow-up (n=16,6)	87.5 percentage of participants	100.0 percentage of participants
Percentage of Participants With Response Based on Clinical Cure and Microbiological Success 6-week follow-up (n=15,6)	93.3 percentage of participants	100.0 percentage of participants

SECONDARY outcome

Timeframe: Day 10

Population: MITT population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species.

A participant had a successful clinical response if there was clinical response of cure or improvement. Clinical response of cure: resolution of signs and symptoms attributed to Candida infection; no additional systemic or oral antifungal treatment required to complete the course of therapy. Clinical response of improvement: significant, but incomplete resolution of signs and symptoms of Candida infection; no additional systemic or oral antifungal treatment required.

Outcome measures

Outcome measures
Measure	Anidulafungin n=24 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=13 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Percentage of Participants With Clinical Response	70.8 percentage of participants Interval 48.9 to 87.4	76.9 percentage of participants Interval 46.2 to 95.0

SECONDARY outcome

Timeframe: 2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)

Population: MITT population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species.

Relapse was defined as any baseline Candida sp. isolated following eradication (documented or presumed) or culture data not available for participants with a clinical response of failure after a previous response of success. Prophylactic treatment with oral antifungal agents was not sufficient to document a relapse.

Outcome measures

Outcome measures
Measure	Anidulafungin n=24 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=13 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Percentage of Participants With Relapse 2-week follow-up	0 percentage of participants	0 percentage of participants
Percentage of Participants With Relapse 6-week follow-up	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: 2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)

Population: MITT population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species.

New Infection: participant presenting with clinical failure with the emergence of new Candida sp. at the original site of infection or at a distant site of infection. Clinical failure: no significant improvement in signs and symptoms, or death due to Candida infection. Participants must have had received at least 3 doses of study drug to be classified as a failure.

Outcome measures

Outcome measures
Measure	Anidulafungin n=24 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=13 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Percentage of Participants With New Infection 2-week follow-up	0 percentage of participants	0 percentage of participants
Percentage of Participants With New Infection 6-week follow-up	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 6-week follow-up (6 weeks after EOT)

Population: A sub-set of MITT population included only those participants who had a positive blood culture for Candida species at baseline.

Negative blood culture referred to absence of Candida sp. in the blood sample of participants who had a positive blood culture at baseline. Time to negative blood culture (days) was calculated as date of first negative blood culture minus first treatment date plus 1.

Outcome measures

Outcome measures
Measure	Anidulafungin n=3 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=4 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Time to Negative Blood Culture	2.0 days Interval 2.0 to 7.0	3.5 days Interval 2.0 to 10.0

SECONDARY outcome

Timeframe: Baseline to EOT (Day 14 to 42), After EOT to 2-week follow-up (2 weeks after EOT), After 2-week follow-up to 6-week follow-up (6 weeks after EOT)

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.

All-cause mortality during study therapy and at follow-up visits reported as unique death at EOT, 2 week follow-up and 6 week follow-up.

Outcome measures

Outcome measures
Measure	Anidulafungin n=26 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=13 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Percentage of Participants With All-cause Mortality After 2-week follow-up to 6-week follow-up	7.7 percentage of participants	0.0 percentage of participants
Percentage of Participants With All-cause Mortality Baseline to EOT	3.8 percentage of participants	15.4 percentage of participants
Percentage of Participants With All-cause Mortality After EOT to 2-week follow-up	15.4 percentage of participants	15.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 6-week follow-up (6 weeks after EOT)

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Time to death (days) was assessed as date of death minus first treatment date plus 1.

Outcome measures

Outcome measures
Measure	Anidulafungin n=26 Participants Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=13 Participants Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Time to Death	23.0 days Interval 6.0 to 67.0	11.5 days Interval 9.0 to 51.0

Adverse Events

Anidulafungin

Serious events: 12 serious events

Other events: 23 other events

Deaths: 0 deaths

Caspofungin

Serious events: 7 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Anidulafungin n=26 participants at risk Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin n=13 participants at risk Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Blood and lymphatic system disorders Haemorrhagic anaemia	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Bradycardia	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac arrest	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	15.4% 2/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	7.7% 2/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Duodenal ulcer	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intestinal fistula	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intra-abdominal haemorrhage	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders General physical health deterioration	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Injury associated with device	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Multi-organ failure	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Abdominal infection	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Abdominal sepsis	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infectious peritonitis	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infectious pleural effusion	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nosocomial infection	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Peptostreptococcus infection	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Peritonitis	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Septic shock	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Tracheobronchitis	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Splenic haematoma	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal failure acute	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pemphigoid	0.00% 0/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 1/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypotension	3.8% 1/26 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/13 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.