Adjunctive Therapeutic Treatment With Human Monoclonal Antibody AR-105 (Aerucin®) in P. Aeruginosa Pneumonia

• Sponsor: Aridis Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03027609
• Collaborator: (none)
• Enrollment: 158
• Locations: 111
• Arms: 2
• Actual Duration (Months): 24.9
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Prospective, double-blind, randomized assessment of the efficacy, safety and pharmacokinetic of Aerucin® as adjunct treatment (in addition to standard of care antibiotics) for pneumonia caused by P. aeruginosa.

Condition or Disease	Intervention/Treatment	Phase
Pseudomonas Aeruginosa Pneumonia	Drug: AR-105; Drug: Placebo	Phase 2

Detailed Description

This is a double-blind, randomized, placebo-controlled study of the human monoclonal antibody (mAb) AR-105 for the adjunctive therapeutic treatment of P. aeruginosa pneumonia in mechanically ventilated subjects. Subjects who are randomized will be treated with either standard of care (SOC) antibiotics plus placebo or SOC antibiotics plus AR-105. The study is being conducted at approximately 100 clinical sites across 17 countries. Subjects who meet all of the inclusion criteria and none of the exclusion criteria are screened by the microbiological culture test and/or rapid diagnostic test of an endotracheal aspirate to confirm the presence of an active P. aeruginosa infection. Following eligibility confirmation, the subject will be randomized in a 1:1 ratio to one of two treatment groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Placebo-controlled, Double-blind, Randomized Study of Aerucin® as Adjunct Therapy to Antibiotics in the Treatment of P. Aeruginosa Pneumonia
• Actual Study Start Date: Mar 29, 2017
• Actual Primary Completion Date: Apr 25, 2019
• Actual Study Completion Date: Apr 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AR-105 One intravenous infusion of AR-105 20mg/'kg	Drug: AR-105; monoclonal antibody; Other Names: Aerubumab Aerucin
Placebo Comparator: Control Matching placebo	Drug: Placebo; matching placebo (+ SOC antibiotics); Other Names: Control (SOC antibiotics)

Outcome Measures

Primary Outcome Measures

1. Clinical Cure on Day 21 [21 days following dosing]

   A summary of the number (%) of patients who were cured on or before Day 21 (micro-ITT population) is provided, by treatment group

Secondary Outcome Measures

1. Clinical Cure on Day 7 [7 days following dosing]

   A summary of the number (%) of patients who were cured on or before Day 7 (micro-ITT population) is provided, by treatment group

2. Clinical Cure on Day 14 [14 days following dosing]

   A summary of the number (%) of patients who were cured on or before Day 14 (micro-ITT population) is provided by treatment group

3. Clinical Cure on Day 28 [28 days following dosing]

   A summary of the number (%) of patients who were cured on or before Day 28 (micro-ITT population) is provided by treatment group

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent

• ≥18 years of age, ≥ 20 years of age (Taiwan only),≥ 19 (S. Korea only)

• pneumonia due to P. aeruginosa

• mechanically-ventilated

• intubated

• APACHE II score between 10 and 35

Exclusion Criteria (main criteria):

• being moribund

• effective antibiotic therapy ≥48 hours

• immunocompromised

• underlying pulmonary disease that may preclude the assessment of a therapeutic response

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site 1	Sacramento	California	United States	95814
2	Research Site 2	San Diego	California	United States	92103
3	Research Site 3	Jacksonville	Florida	United States	32209
4	Research Site 4	Tampa	Florida	United States	33606
5	Research Site 5	Chicago	Illinois	United States	60611
6	Research Site 6	Lexington	Kentucky	United States	40536
7	Research Site 7	Detroit	Michigan	United States	48201
8	Research Site 8	Detroit	Michigan	United States	48201
9	Research Site 9	Royal Oak	Michigan	United States	48073
10	Research Site 10	Saint Louis	Missouri	United States	63110
11	Research Site	Saint Louis	Missouri	United States	63141
12	Research Site	Hackensack	New Jersey	United States	02601
13	Research Site	Durham	North Carolina	United States	27710
14	Research Site	Columbus	Ohio	United States	43215
15	Research Site	Adelaide		Australia	5000
16	Research Site	Woolloongabba		Australia	QLD 4102
17	Research Site	Brest		Belarus	224027
18	Research Site	Gomel		Belarus	246027
19	Research Site	Grodno		Belarus	230030
20	Research Site	Minsk		Belarus	220049
21	Research Site	Minsk		Belarus	223041
22	Research Site	Vitebsk		Belarus	210037
23	Research Site	Brussels		Belgium	1090
24	Research Site	Brussels		Belgium	11070
25	Research Site	Brussels		Belgium	1200
26	Research Site	Dinant		Belgium	5500
27	Research Site	Liège		Belgium	4000
28	Research Site	Yvoir		Belgium	5530
29	Research Site	Brno		Czechia	65691
30	Research Site	Plzen		Czechia	30460
31	Research Site	Praha		Czechia	10034
32	Research Site	Praha		Czechia	12808
33	Research Site	Praha		Czechia	16902
34	Research Site	Teplice		Czechia	41529
35	Research Site	Zlín		Czechia	76275
36	Research Site	Angers		France	49933
37	Research Site	Argenteuil		France	95107
38	Research Site	Colombes		France	92701
39	Research Site	La Roche-sur-Yon		France	85925
40	Research Site	Le Chesnay		France	78157
41	Research Site	Lille		France	59037
42	Research Site	Limoges		France	87042
43	Research Site	Lyon		France	69004
44	Research Site	Lyon		France	69677
45	Research Site	Nantes		France	44093
46	Research Site 1	Paris		France	75013
47	Research Site 2	Paris		France	75013
48	Research Site	Paris		France	75013
49	Research Site	Pierre-Bénite		France	69495
50	Research Site	Pontoise		France	95303
51	Research Site	Strasbourg		France	67091
52	Research Site	Tourcoing		France	59208
53	Research Site	Tours		France	37044
54	Research Site 1	Kutaisi		Georgia	4600
55	Research Site 2	Kutaisi		Georgia	4600
56	Research Site	Tbilisi		Georgia	0144
57	Research Site 1	Athens		Greece	10676
58	Research Site 2	Athens		Greece	11527
59	Research Site 1	Larissa		Greece	41110
60	Research Site 2	Larissa		Greece	41221
61	Research Site 3	Budapest		Hungary	1122
62	Research Site 2	Budapest		Hungary	H-1082
63	Research Site 1	Budapest		Hungary	H-1134
64	Research Site	Debrecen		Hungary	H-4032
65	Research Site	Nyiregyhaza		Hungary	H-4400
66	Research Site 1	Gyeonggi-do		Korea, Republic of	425-707
67	Research Site 2	Gyeonggi-do		Korea, Republic of	442-723
68	Research Site 2	Seoul		Korea, Republic of	02841
69	Research Site 1	Seoul		Korea, Republic of	03080
70	Research Site 3	Seoul		Korea, Republic of	05505
71	Research Site 4	Seoul		Korea, Republic of	07441
72	Research Site	Wŏnju		Korea, Republic of	26426
73	Research Site 1	Guadalajara		Mexico	44280
74	Research Site 2	Guadalajara		Mexico	44760
75	Research Site	Monterrey		Mexico	64460
76	Research Site	Lima		Peru	15072
77	Research Site	Miraflores		Peru	15074
78	Research Site	San Martín De Porres		Peru	15102
79	Research Site	Opole		Poland	45-418
80	Research Site	Warsaw		Poland	02-781
81	Research Site	Krasnodar		Russian Federation	350012
82	Research Site	Krasnoyarsk		Russian Federation	660022
83	Research Site 2	Novosibirsk		Russian Federation	119049
84	Research Site 3	Novosibirsk		Russian Federation	630051
85	Research Site 1	Novosibirsk		Russian Federation	630075
86	Research Site 2	Saint Petersburg		Russian Federation	192242
87	Research Site 3	Saint Petersburg		Russian Federation	196067
88	Research Site 4	Saint Petersburg		Russian Federation	196247
89	Research Site 1	Saint Petersburg		Russian Federation	197706
90	Research Site	Tomsk		Russian Federation	634050
91	Research Site 1	Barcelona		Spain	08036
92	Research Site 2	Barcelona		Spain	08221
93	Research Site 3	Barcelona		Spain	08221
94	Research Site 4	Barcelona		Spain	0897
95	Research Site	Madrid		Spain	28040
96	Research Site	Mataró		Spain	08034
97	Research Site	Oviedo		Spain	33011
98	Research Site	Santander		Spain	39008
99	Research Site	Tarragona		Spain	43005
100	Research Site 1	Kaohsiung		Taiwan	80756
101	Research Site 2	Kaohsiung		Taiwan	81362
102	Research Site 2	Taichung		Taiwan	40447
103	Research Site 1	Taichung		Taiwan	40705
104	Research Site	Tainan		Taiwan	71004
105	Research Site 1	Taipei		Taiwan	10002 R.O.C
106	Research Site 4	Taipei		Taiwan	10449
107	Research Site 2	Taipei		Taiwan	11217
108	Research Site 3	Taipei		Taiwan	114
109	Research Site	Ivano-Frankivs'k		Ukraine	76008
110	Research Site	Kiev		Ukraine	01034
111	Research Site	Lviv		Ukraine	79059

Sponsors and Collaborators

• Aridis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 9, 2018
• Statistical Analysis Plan - Aug 13, 2019

More Information

Publications

None provided.

• Responsible Party: Aridis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03027609
• Other Study ID Numbers: AR-105-002
• First Posted: Jan 23, 2017
• Last Update Posted: Mar 17, 2022
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Aridis Pharmaceuticals, Inc.: Pseudomonas aeruginosa; pneumonia
• Additional relevant MeSH terms: Pneumonia; Pseudomonas Infections; Anti-Bacterial Agents

Study Results

Participant Flow

Arm/Group Title	AR-105	Control
Arm/Group Description	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody	Matching placebo placebo: matching placebo
Period Title: Overall Study
STARTED	79	79
COMPLETED	49	62
NOT COMPLETED	30	17

Baseline Characteristics

Arm/Group Title	AR-105	Control	Total
Arm/Group Description	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody	Matching placebo placebo: matching placebo	Total of all reporting groups
Overall Participants	79	79	158
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (13.83)	61.2 (15.58)	62.3 (14.73)
Age, Customized (Count of Participants)
Age </= 64 years	40 50.6%	39 49.4%	79 50%
Age > 64 years	39 49.4%	40 50.6%	79 50%
Sex: Female, Male (Count of Participants)
Female	17 21.5%	21 26.6%	38 24.1%
Male	62 78.5%	58 73.4%	120 75.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 5.1%	4 5.1%	8 5.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 2.5%	1 1.3%	3 1.9%
White	73 92.4%	74 93.7%	147 93%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Hungary	10 12.7%	8 10.1%	18 11.4%
United States	3 3.8%	4 5.1%	7 4.4%
Czechia	5 6.3%	5 6.3%	10 6.3%
Ukraine	6 7.6%	11 13.9%	17 10.8%
Belarus	7 8.9%	5 6.3%	12 7.6%
Russia	21 26.6%	21 26.6%	42 26.6%
Spain	4 5.1%	3 3.8%	7 4.4%
Greece	5 6.3%	2 2.5%	7 4.4%
Belgium	3 3.8%	3 3.8%	6 3.8%
Taiwan	2 2.5%	3 3.8%	5 3.2%
Georgia	1 1.3%	0 0%	1 0.6%
France	10 12.7%	14 17.7%	24 15.2%
South Korea	2 2.5%	0 0%	2 1.3%
World Regions (Count of Participants)
Americas	3 3.8%	4 5.1%	7 4.4%
Eastern Europe	50 63.3%	50 63.3%	100 63.3%
Western Europe	22 27.8%	22 27.8%	44 27.8%
Asia	4 5.1%	3 3.8%	7 4.4%

Outcome Measures

1. Primary Outcome

Title	Clinical Cure on Day 21
Description	A summary of the number (%) of patients who were cured on or before Day 21 (micro-ITT population) is provided, by treatment group
Time Frame	21 days following dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AR-105	Control
Arm/Group Description	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody	Matching placebo placebo: matching placebo
Measure Participants	70	67
Observed Cured	34 43%	37 46.8%
Imputed Cured	6 7.6%	5 6.3%
Not Cured	25 31.6%	20 25.3%
Reinfection same pathogen	5 6.3%	2 2.5%
New Infection Different Pathogen	0 0%	3 3.8%
New infection Unknown pathogen	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AR-105, Control
	Comments
	Type of Statistical Test	Superiority
	Comments	comparison between the treatment and placebo
Statistical Test of Hypothesis	p-Value	0.6154
	Comments	P-value was obtained with the stratified CMH test adjusted for baseline randomization strata
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-5.54
	Confidence Interval	(2-Sided) 95%; -21.9 to 10.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Clinical Cure on Day 7
Description	A summary of the number (%) of patients who were cured on or before Day 7 (micro-ITT population) is provided, by treatment group
Time Frame	7 days following dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AR-105	Control
Arm/Group Description	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody	Matching placebo placebo: matching placebo
Measure Participants	70	67
Cured Observed	16 20.3%	18 22.8%
Cured Imputed	0 0%	0 0%
Not Cured	52 65.8%	47 59.5%
Re-infection Same Pathogen	1 1.3%	0 0%
New Infection Different Pathogen	1 1.3%	1 1.3%
New Infection Unknown Pathogen	0 0%	1 1.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AR-105, Control
	Comments	Comparison between the treatment and placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8426
	Comments	P-value was obtained with the stratified CMH test adjusted for baseline randomization strata
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	4.01
	Confidence Interval	(2-Sided) 95%; -18.5 to 10.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Clinical Cure on Day 14
Description	A summary of the number (%) of patients who were cured on or before Day 14 (micro-ITT population) is provided by treatment group
Time Frame	14 days following dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AR-105	Control
Arm/Group Description	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody	Matching placebo placebo: matching placebo
Measure Participants	70	67
Observed Cured	36 45.6%	31 39.2%
Imputed Cured	1 1.3%	2 2.5%
Not Cured	29 36.7%	30 38%
Reinfection same pathogen	1 1.3%	0 0%
New Infection Different Pathogen	2 2.5%	4 5.1%
New infection Unknown Pathogen	1 1.3%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AR-105, Control
	Comments	Comparison between the treatment and placebo
	Type of Statistical Test	Superiority
	Comments	comparison between the treatment and placebo
Statistical Test of Hypothesis	p-Value	0.3562
	Comments	P-value was obtained with the stratified CMH test adjusted for baseline randomization strata
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	P value CMH
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -13.1 to 20.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Clinical Cure on Day 28
Description	A summary of the number (%) of patients who were cured on or before Day 28 (micro-ITT population) is provided by treatment group
Time Frame	28 days following dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AR-105	Control
Arm/Group Description	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody	Matching placebo placebo: matching placebo
Measure Participants	70	67
Observed Cured	35 44.3%	38 48.1%
Imputed Cured	9 11.4%	6 7.6%
Not Cured	23 29.1%	16 20.3%
Reinfection same pathogen	3 3.8%	3 3.8%
New Infection Different Pathogen	0 0%	4 5.1%
New infection Unknown Pathogen	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AR-105, Control
	Comments
	Type of Statistical Test	Superiority
	Comments	Comparison between the treatment and placebo
Statistical Test of Hypothesis	p-Value	0.8472
	Comments	P-value was obtained with the stratified CMH test adjusted for baseline randomization strata
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	P value CMH
	Estimated Value	-2.81
	Confidence Interval	(2-Sided) 95%; -18.9 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Post-Hoc Outcome

Title	Absolute Difference Clinical Cure at Day 14 and 21 for Study 1
Description	Difference in percentage of clinical cure rates between the two treatment groups
Time Frame	Up to Day 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subset AR-105 Study1	Subset Placebo Study1
Arm/Group Description	Using the appropriate clinical severity, level of CRP and adequate antibiotic criteria, patients were subdivided into subgroups to identify a pattern in the clinical cure rates in both treatment groups. The results suggest the presence of heterogeneity of factors influencing the clinical cure rates, where only a quite small sample is evaluable. A subset of patients had the following characteristics and were found to belong to appropriate clinical Severity inadequate antibiotic regimen and lower 3rd quartile of level of CRP	Using the appropriate clinical severity, level of CRP and adequate antibiotic criteria, patients were subdivided into subgroups to identify a pattern in the clinical cure rates in both treatment groups. The results suggest the presence of heterogeneity of factors influencing the clinical cure rates, where only a quite small sample is evaluable. A subset of patients had the following characteristics and were found to belong to appropriate clinical Severity inadequate antibiotic regimen and lower 3rd quartile of level of CRP
Measure Participants	9	18
Cured Day 14	6 7.6%	8 10.1%
Cured Day 21	7 8.9%	10 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AR-105, Control
	Comments	Data for Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4616
	Comments	Marginally statistically significant only if p<0.1
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	22.3
	Confidence Interval	(2-Sided) 95%; -16.2 to 60.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AR-105, Control
	Comments	Data for Day 21
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4053
	Comments	Data for Day 21
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	22.3
	Confidence Interval	(2-Sided) 95%; -13.3 to 57.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Post-Hoc Outcome

Title	Absolute Difference Clinical Cure at Day 14 and 21 for Study 2
Description	Difference in percentage of clinical cure rates between the two treatment groups
Time Frame	Up to Day 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subset AR-105 Study2	Subset Placebo Study2
Arm/Group Description	Using the appropriate clinical severity, level of CRP and adequate antibiotic criteria, patients were subdivided into subgroups to identify a pattern in the clinical cure rates in both treatment groups. The results suggest the presence of heterogeneity of factors influencing the clinical cure rates, where only a quite small sample is evaluable. A subset of patients had the following characteristics and were found to belong to appropriate clinical Severity inadequate antibiotic regimen and lower 3rd quartile of level of CRP	Using the appropriate clinical severity, level of CRP and adequate antibiotic criteria, patients were subdivided into subgroups to identify a pattern in the clinical cure rates in both treatment groups. The results suggest the presence of heterogeneity of factors influencing the clinical cure rates, where only a quite small sample is evaluable. A subset of patients had the following characteristics and were found to belong to appropriate clinical Severity inadequate antibiotic regimen and lower 3rd quartile of level of CRP
Measure Participants	3	7
Cured Day 14	2 2.5%	2 2.5%
Cured Day 21	2 2.5%	3 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AR-105, Control
	Comments	Data for Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0833
	Comments	Marginally statistically significant only if p<0.1
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	38.1
	Confidence Interval	(2-Sided) 90%; -14.8 to 90.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AR-105, Control
	Comments	Data for Day 21
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5151
	Comments	Data for Day 21
	Method	Chi-squared
	Comments	Marginally statistically significant only if p<0.1 Day 21
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	23.8
	Confidence Interval	(2-Sided) 90%; -30.5 to 78.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	1 month: from administration day (Day 0) up to Day 28 (28 days after administration)
Arm/Group Title	AR-105		Control
Arm/Group Description	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody		Matching placebo placebo: matching placebo
All Cause Mortality
	AR-105		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/79 (31.6%)		13/79 (16.5%)
Serious Adverse Events
	AR-105		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/79 (45.6%)		22/79 (27.8%)
Blood and lymphatic system disorders
Anaemia	1/79 (1.3%)		0/79 (0%)
Cardiac disorders
Acute left ventricular failure	0/79 (0%)		1/79 (1.3%)
Acute myocardial infarction	0/79 (0%)		1/79 (1.3%)
Atrial fibrillation	1/79 (1.3%)		0/79 (0%)
Cardiac arrest	2/79 (2.5%)		1/79 (1.3%)
Cardiac failure	0/79 (0%)		1/79 (1.3%)
Cardiac failure acute	3/79 (3.8%)		1/79 (1.3%)
Cardiac failure congestive	1/79 (1.3%)		0/79 (0%)
Cardio-respiratory arrest	1/79 (1.3%)		1/79 (1.3%)
Cardiopulmonary failure	1/79 (1.3%)		1/79 (1.3%)
Cardiovascular insufficiency	1/79 (1.3%)		0/79 (0%)
Myocardial infarction	1/79 (1.3%)		1/79 (1.3%)
Rhythm idioventricular	0/79 (0%)		1/79 (1.3%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula	1/79 (1.3%)		0/79 (0%)
Gastrointestinal disorders
Colitis ischaemic	0/79 (0%)		1/79 (1.3%)
Duodenal ulcer	0/79 (0%)		1/79 (1.3%)
Gastric ulcer	0/79 (0%)		1/79 (1.3%)
Gastrointestinal haemorrhage	0/79 (0%)		2/79 (2.5%)
Lower gastrointestinal haemorrhage	1/79 (1.3%)		0/79 (0%)
Oesophageal ulcer	0/79 (0%)		1/79 (1.3%)
Upper gastrointestinal haemorrhage	2/79 (2.5%)		0/79 (0%)
General disorders
Cardiac death	0/79 (0%)		1/79 (1.3%)
Multiple organ dysfunction syndrome	7/79 (8.9%)		4/79 (5.1%)
Systemic inflammatory response syndrome	0/79 (0%)		1/79 (1.3%)
Infections and infestations
Abdominal abscess	0/79 (0%)		2/79 (2.5%)
Bacteraemia	1/79 (1.3%)		0/79 (0%)
Cholecystitis infective	1/79 (1.3%)		0/79 (0%)
Fungal sepsis	0/79 (0%)		1/79 (1.3%)
Lung abscess	0/79 (0%)		1/79 (1.3%)
Pneumonia	3/79 (3.8%)		1/79 (1.3%)
Pneumonia bacterial	0/79 (0%)		1/79 (1.3%)
Pneumonia cytomegaloviral	1/79 (1.3%)		0/79 (0%)
Pneumonia pseudomonal	1/79 (1.3%)		0/79 (0%)
Pneumonia staphylococcal	0/79 (0%)		1/79 (1.3%)
Postoperative wound infection	0/79 (0%)		1/79 (1.3%)
Sepsis	3/79 (3.8%)		0/79 (0%)
Septic shock	5/79 (6.3%)		3/79 (3.8%)
Systemic candida	0/79 (0%)		1/79 (1.3%)
Injury, poisoning and procedural complications
Brain herniation	3/79 (3.8%)		0/79 (0%)
Gastrointestinal stoma complication	0/79 (0%)		1/79 (1.3%)
Investigations
Transaminases increased	1/79 (1.3%)		0/79 (0%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/79 (1.3%)		0/79 (0%)
Nervous system disorders
Brain oedema	3/79 (3.8%)		0/79 (0%)
Coma	1/79 (1.3%)		0/79 (0%)
Neuropathy peripheral	0/79 (0%)		1/79 (1.3%)
Renal and urinary disorders
Acute kidney injury	1/79 (1.3%)		0/79 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	2/79 (2.5%)		0/79 (0%)
Acute respiratory failure	0/79 (0%)		1/79 (1.3%)
Chronic obstructive pulmonary disease	1/79 (1.3%)		0/79 (0%)
Pneumothorax	1/79 (1.3%)		1/79 (1.3%)
Pulmonary embolism	3/79 (3.8%)		2/79 (2.5%)
Respiratory distress	0/79 (0%)		2/79 (2.5%)
Respiratory failure	5/79 (6.3%)		0/79 (0%)
Vascular disorders
Circulatory Collapse	1/79 (1.3%)		0/79 (0%)
Haemodynamic instability	0/79 (0%)		1/79 (1.3%)
Shock	1/79 (1.3%)		0/79 (0%)
Shock haemorrhagic	1/79 (1.3%)		0/79 (0%)
Arterial rupture	1/79 (1.3%)		0/79 (0%)
Other (Not Including Serious) Adverse Events
	AR-105		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/79 (92.4%)		73/79 (92.4%)
Blood and lymphatic system disorders
Anaemia	16/79 (20.3%)		13/79 (16.5%)
Thrombocytopenia	6/79 (7.6%)		1/79 (1.3%)
Cardiac disorders
Atrial fibrillation	6/79 (7.6%)		7/79 (8.9%)
Bradycardia	2/79 (2.5%)		4/79 (5.1%)
Gastrointestinal disorders
Constipation	6/79 (7.6%)		2/79 (2.5%)
Diarrhoea	5/79 (6.3%)		13/79 (16.5%)
Nausea	3/79 (3.8%)		4/79 (5.1%)
General disorders
Multiple organ dysfunction syndrome	10/79 (12.7%)		4/79 (5.1%)
Oedema peripheral	1/79 (1.3%)		4/79 (5.1%)
Pyrexia	5/79 (6.3%)		3/79 (3.8%)
Infections and infestations
Cystitis	4/79 (5.1%)		4/79 (5.1%)
Pneumonia	5/79 (6.3%)		5/79 (6.3%)
Sepsis	5/79 (6.3%)		0/79 (0%)
Septic shock	6/79 (7.6%)		5/79 (6.3%)
Tracheobronchitis	4/79 (5.1%)		2/79 (2.5%)
Urinary tract infection	1/79 (1.3%)		6/79 (7.6%)
Investigations
Alanine aminotransferase increased	0/79 (0%)		6/79 (7.6%)
Aspartate aminotransferase increased	0/79 (0%)		6/79 (7.6%)
Metabolism and nutrition disorders
Hyperkalaemia	6/79 (7.6%)		4/79 (5.1%)
Hypernatraemia	4/79 (5.1%)		1/79 (1.3%)
Hypokalaemia	12/79 (15.2%)		6/79 (7.6%)
Hypovolaemia	4/79 (5.1%)		3/79 (3.8%)
Nervous system disorders
Agitation	4/79 (5.1%)		2/79 (2.5%)
Brain oedema	5/79 (6.3%)		0/79 (0%)
Delirium	4/79 (5.1%)		2/79 (2.5%)
Insomnia	4/79 (5.1%)		3/79 (3.8%)
Renal and urinary disorders
Acute kidney injury	4/79 (5.1%)		4/79 (5.1%)
Respiratory, thoracic and mediastinal disorders
Hydrothorax	5/79 (6.3%)		3/79 (3.8%)
Pneumothorax	4/79 (5.1%)		2/79 (2.5%)
Respiratory failure	5/79 (6.3%)		0/79 (0%)
Tachypnoea	4/79 (5.1%)		3/79 (3.8%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	6/79 (7.6%)		9/79 (11.4%)
Vascular disorders
Hypotension	14/79 (17.7%)		9/79 (11.4%)

Limitations/Caveats

A post-hoc analysis was performed on the data reviewed by the AC, using the appropriate clinical severity, adequate antibiotic criteria and the inflammatory status of the patient (level of C-reactive protein [CRP]).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.