UMIN-CTR Clinical Trial

Basic information
Public title	A prospective observational study of patients with advanced cancer for the evaluation of checkpoint inhibitor-associated cardiovascular immune-related adverse events
Acronym	AWARENESS-irAE registry
Scientific Title	A prospective observational study of patients with advanced cancer for the evaluation of checkpoint inhibitor-associated cardiovascular immune-related adverse events
Scientific Title:Acronym	AWARENESS-irAE registry
Region	Japan

Condition
Condition	Advanced non-small-cell lung cancer and advanced gastric cancer which are indications for anti-cytotoxic T-lymphocyte-associated antigen-4, anti-programmed death-1, and anti-programmed death-ligand 1 antibodies.
Classification by specialty	Gastroenterology Cardiology Pneumology Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The prevalence of cardiovascular immune-related adverse events, including immune-mediated myocarditis, remains unclear because most immunotherapy trials have been conducted without the inclusion of routine cardiac monitoring.
Basic objectives2	Others
Basic objectives -Others	Thus, this registry aims to evaluate the incidence, risk factors, clinical presentation, treatments, and outcomes of both subclinical and clinically evident cardiovascular immune-related adverse events related to immune checkpoint inhibitors. Furthermore, this registry aims to confirm the suitability of regular monitoring for immune-mediated myocarditis using serial electrocardiograms and serum creatine kinase isoenzyme MB (CK-MB), brain natriuretic peptide (BNP), and troponin T in patients receiving immune checkpoint inhibitors. This study intends to assess whether reviewing serial electrocardiograms and serum CK-MB, BNP, and troponin T levels could facilitate the detection of the development of cardiac toxicity before left ventricular dysfunction becomes evident on echocardiography or before the onset of clinical symptoms.
Trial characteristics_1	Exploratory
Trial characteristics_2	Others
Developmental phase	Not applicable

Assessment
Primary outcomes	Primary outcomes: Subclinical or smoldering cardiac toxicity, defined as a composite of BNP elevation up to 200 pg/mL, positive troponin T, elevated CK-MB, new-onset morphological electrocardiogram abnormalities, or a reduction in the left ventricular ejection fraction of >10% compared to baseline.
Key secondary outcomes	Secondary outcomes: (1) clinically apparent acute myocarditis; (2) acute heart failure, cardiogenic shock of unknown etiology, or symptomatic deterioration in at least one New York Heart Association functional class; (3) lethal arrhythmia, including advanced or complete AV block, ventricular tachycardia, or fibrillation; (4) cardiac death, new-onset acute coronary syndromes, any coronary revascularization procedure; (5) other immune-related adverse events, including dermatological, ophthalmological, neurological, hematological, gastrointestinal, endocrine, genitourinary, respiratory, and musculoskeletal adverse events; and (6) all-cause death.

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients with advanced non-small-cell lung cancer and advanced gastric cancer which are indications for anti-cytotoxic T-lymphocyte-associated antigen-4, anti-programmed death-1, and anti-programmed death-ligand 1 antibodies.
Key exclusion criteria	Patients who undergo hemodialysis or have anaphylactic reactions to immune checkpoint inhibitors
Target sample size	200

Research contact person
Name of lead principal investigator	1st name Tsuyoshi Middle name Last name Isawa
Organization	Sendai Kousei Hospital
Division name	Cardiology
Zip code	980-0873
Address	Hirosemachi 4-15, Sendai, Japan
TEL	022-222-6181
Email	isa_tsuyo@yahoo.co.jp

Public contact
Name of contact person	1st name Tsuyoshi Middle name Last name Isawa
Organization	Sendai Kousei Hospital
Division name	Cardiology
Zip code	980-0873
Address	Hirosemachi 4-15, Sendai, Japan
TEL	022-222-6181
Homepage URL
Email	isa_tsuyo@yahoo.co.jp

Sponsor
Institute	Frontline Immunotherapy Team, Sendai Kousei Hospital
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Sendai Kousei Hospital
Address	Hirosemachi 4-15, Sendai, Japan
Tel	022-2226-1818
Email	heartcenter@st.cat-v.ne.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	Sendai Kousei Hospital (Miyagi prefecture)

Other administrative information
Date of disclosure of the study information	2018 Year 05 Month 26 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications	https://academic.oup.com/oncolo/article/27/5/e410/6555104
Number of participants that the trial has enrolled	129
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2022 Year 03 Month 28 Day
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Main results already published
Date of protocol fixation	2018 Year 05 Month 16 Day
Date of IRB	2018 Year 05 Month 16 Day
Anticipated trial start date	2018 Year 05 Month 16 Day
Last follow-up date	2022 Year 05 Month 16 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	This is a prospective observational study of patients with advanced cancer for the evaluation of checkpoint inhibitor-associated cardiovascular immune-related adverse events.

Management information
Registered date	2018 Year 05 Month 26 Day
Last modified on	2022 Year 05 Month 31 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037322