Trial Outcomes & Findings for Instylla HES Hypervascular Tumor Pivotal Study (NCT NCT04523350)

NCT ID: NCT04523350

Last Updated: 2026-06-29

Results Overview

Stasis of flow defined as absence of contrast flow within the targeted tumor feeding vessel

Recruitment status

COMPLETED

Study phase

Target enrollment

150 participants

Primary outcome timeframe

Immediately post-embolization procedure

Results posted on

2026-06-29

Participant Flow

Patients were treated between March 5, 2021, and May 1, 2024. There were 22 investigational sites both in United States (US) and outside of US (OUS). Investigational sites included hospitals and office-based labs (OBLs).

Participants were prospectively reviewed against inclusion and exclusion criteria prior to the index procedure. There was no wash-out or run-in for this study.

Participant milestones

Participant milestones
Measure	Instylla Hydrogel Embolic System (HES) Subjects were treated using Instylla HES.	Control Interventions were in accordance with the investigators' standard of care treatment and included bland embolization products, ethanol, or conventional TACE in combination with lipiodol. Drug-eluting beads are prohibited from use in this protocol.
Overall Study STARTED	102	48
Overall Study COMPLETED	88	41
Overall Study NOT COMPLETED	14	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Instylla HES Hypervascular Tumor Pivotal Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Instylla Hydrogel Embolic System (HES) n=102 Participants Subjects were treated using Instylla HES	Control n=48 Participants Interventions were in accordance with the investigators' standard of care treatment and included bland embolization products, ethanol, or conventional TACE in combination with lipiodol. Drug-eluting beads are prohibited from use in this protocol.	Total n=150 Participants Total of all reporting groups
Age, Continuous	65.6 years STANDARD_DEVIATION 12.37 • n=9 Participants	65.1 years STANDARD_DEVIATION 14.09 • n=27 Participants	65.4 years STANDARD_DEVIATION 12.90 • n=267 Participants
Sex: Female, Male Female	51 Participants n=9 Participants	33 Participants n=27 Participants	84 Participants n=267 Participants
Sex: Female, Male Male	51 Participants n=9 Participants	15 Participants n=27 Participants	66 Participants n=267 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=9 Participants	0 Participants n=27 Participants	1 Participants n=267 Participants
Race (NIH/OMB) Asian	7 Participants n=9 Participants	3 Participants n=27 Participants	10 Participants n=267 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=9 Participants	0 Participants n=27 Participants	1 Participants n=267 Participants
Race (NIH/OMB) Black or African American	12 Participants n=9 Participants	2 Participants n=27 Participants	14 Participants n=267 Participants
Race (NIH/OMB) White	77 Participants n=9 Participants	40 Participants n=27 Participants	117 Participants n=267 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	2 Participants n=27 Participants	2 Participants n=267 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=9 Participants	1 Participants n=27 Participants	5 Participants n=267 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=9 Participants	6 Participants n=27 Participants	21 Participants n=267 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	87 Participants n=9 Participants	42 Participants n=27 Participants	129 Participants n=267 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=27 Participants	0 Participants n=267 Participants
Region of Enrollment United States	85 Participants n=9 Participants	38 Participants n=27 Participants	123 Participants n=267 Participants
Region of Enrollment Australia	0 Participants n=9 Participants	1 Participants n=27 Participants	1 Participants n=267 Participants
Region of Enrollment Canada	17 Participants n=9 Participants	9 Participants n=27 Participants	26 Participants n=267 Participants

PRIMARY outcome

Timeframe: Immediately post-embolization procedure

Population: Per protocol, subjects could contribute more than one target vessel for embolization; however, only vessels pre-specified for embolization before randomization were included in the primary effectiveness analysis. Consequently, the primary effectiveness analysis was based on 132 vessels in 97 subjects treated with HES and 66 vessels in 48 subjects treated with Standard of Care.

Stasis of flow defined as absence of contrast flow within the targeted tumor feeding vessel

Outcome measures

Outcome measures
Measure	Instylla Hydrogel Embolic System (HES) n=132 Target vessels Subjects were treated using Instylla HES	Control n=66 Target vessels Interventions were in accordance with the investigators' standard of care treatment and included bland embolization products, ethanol, or conventional TACE in combination with lipiodol. Drug-eluting beads are prohibited from use in this protocol.
Primary Effectiveness Endpoint: Delivery of the Embolic Agent to the Index Tumor Feeding Vessel With Stasis of Flow as Determined by an Independent Radiologist Via Comparison of the Pre and Final Post Procedure Images	117 Target vessels	51 Target vessels

PRIMARY outcome

Timeframe: 30 days post-embolization procedure

Population: Freedom from major adverse events for Embrace HES subjects through 30 days post-index procedure compared to a literature derived performance goal. The control group was not used or analyzed as a part of this study endpoint. Only the HES subjects were compared to the literature derived performance goal.

Freedom from major adverse events through 30 days post-index procedure compared to a literature derived performance goal

Outcome measures

Outcome measures
Measure	Instylla Hydrogel Embolic System (HES) n=96 Participants Subjects were treated using Instylla HES	Control Interventions were in accordance with the investigators' standard of care treatment and included bland embolization products, ethanol, or conventional TACE in combination with lipiodol. Drug-eluting beads are prohibited from use in this protocol.
Primary Safety Endpoint: Freedom From Major Adverse Events Through 30 Days Post-index Procedure	1 Participants	—

Adverse Events

Instylla HES

Serious events: 31 serious events

Other events: 82 other events

Deaths: 5 deaths

Control

Serious events: 9 serious events

Other events: 35 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Instylla HES n=101 participants at risk The Instylla HES group was embolized using Instylla HES in place of the Investigator's standard embolization products.	Control n=49 participants at risk Interventions were in accordance with the investigators' standard of care treatment and included bland embolization products, ethanol, or conventional TACE in combination with lipiodol. Drug-eluting beads are prohibited from use in this protocol.
Blood and lymphatic system disorders Anaemia	5.0% 5/101 • Number of events 6 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	2.0% 1/49 • Number of events 1 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Gastrointestinal disorders Abdominal pain	32.7% 33/101 • Number of events 41 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	26.5% 13/49 • Number of events 15 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Gastrointestinal disorders Constipation	6.9% 7/101 • Number of events 7 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	8.2% 4/49 • Number of events 5 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Gastrointestinal disorders Diarrhoea	6.9% 7/101 • Number of events 7 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	2.0% 1/49 • Number of events 1 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Gastrointestinal disorders Nausea	11.9% 12/101 • Number of events 15 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	6.1% 3/49 • Number of events 3 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Gastrointestinal disorders Vomiting	5.9% 6/101 • Number of events 7 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	4.1% 2/49 • Number of events 2 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
General disorders Fatigue	8.9% 9/101 • Number of events 9 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	10.2% 5/49 • Number of events 6 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
General disorders Non-cardiac chest pain	5.9% 6/101 • Number of events 6 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	2.0% 1/49 • Number of events 1 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Infections and infestations Covid-19	5.0% 5/101 • Number of events 5 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	4.1% 2/49 • Number of events 2 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Injury, poisoning and procedural complications Post embolisation syndrome	10.9% 11/101 • Number of events 13 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	8.2% 4/49 • Number of events 4 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Musculoskeletal and connective tissue disorders Back pain	5.9% 6/101 • Number of events 6 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	4.1% 2/49 • Number of events 2 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Musculoskeletal and connective tissue disorders Pain in extremity	8.9% 9/101 • Number of events 13 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	6.1% 3/49 • Number of events 6 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Nervous system disorders Dizziness	5.0% 5/101 • Number of events 5 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	4.1% 2/49 • Number of events 2 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.9% 8/101 • Number of events 9 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	6.1% 3/49 • Number of events 3 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.

Additional Information

Lynn Morrison

Instylla

Phone: 408-592-8292

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Instylla HES n=101 participants at risk The Instylla HES group was embolized using Instylla HES in place of the Investigator's standard embolization products.	Control n=49 participants at risk Interventions were in accordance with the investigators' standard of care treatment and included bland embolization products, ethanol, or conventional TACE in combination with lipiodol. Drug-eluting beads are prohibited from use in this protocol.
Blood and lymphatic system disorders Blood and lymphatic system disorders	3.0% 3/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Cardiac disorders Cardiac disorders	0.00% 0/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	2.0% 1/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Endocrine disorders Endocrine Disorders	0.99% 1/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Gastrointestinal disorders Gastrointestinal disorders	7.9% 8/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	2.0% 1/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
General disorders General disorders and administration site conditions	5.0% 5/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	8.2% 4/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Hepatobiliary disorders Hepatobiliary disorders	0.99% 1/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Immune system disorders Immune system disorders	2.0% 2/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Infections and infestations Infections and infestations	5.9% 6/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	6.1% 3/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	5.9% 6/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Investigations Investigations	0.99% 1/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Metabolism and nutrition disorders Metabolism and nutrition disorders	4.0% 4/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	2.0% 1/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	0.99% 1/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	2.0% 2/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	6.1% 3/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Nervous system disorders Nervous system disorders	3.0% 3/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	4.1% 2/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Pregnancy, puerperium and perinatal conditions Pregnancy, puerperium and perinatal conditions	0.99% 1/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Renal and urinary disorders Renal and urinary disorders	2.0% 2/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	4.0% 4/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	0.00% 0/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.
Vascular disorders Vascular disorders	2.0% 2/101 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.	2.0% 1/49 • from enrollment until end of follow-up, up to 180 days AEs and SAEs were analyzed using the Safety Population. The Safety Population included all randomized, treated subjects. Subjects were analyzed for safety based on the treatment received. All-cause mortality was analyzed using the Intent to Treat Population, which includes all enrolled subjects who were randomized.