Clinical trial NCT04398992: Additive Anti-inflammatory Action for Aortopathy & Arteriopathy
Official title: Chinese Registry of Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) Protocol: Rationale, Design and Methodology
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Acute Aortic Syndrome
Keywords: Acute Aortic Syndrome
Lead sponsor: Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Beijing Anzhen Hospital
First posted: 2020-05-22
Enrollment: 10000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chinese patients suffering AAS

Brief summary: Acute aortic syndrome (AAS) is a life-threatening condition. Inflammation plays a key role in the pathogenesis, development and progression of AAS, and is associated with significant mortality and morbidity. Understanding the inflammatory responses and inflammation resolutions is essential for an appropriate management of AAS.

Twenty Chinese cardiovascular centers have collaborated to create a multicenter observational registry (named Chinese registry of Additive Anti-inflammatory Action for Aortopathy \& Arteriopathy \[5A\]), with consecutive enrollment of adult patients who underwent surgery for AAS that was started on Jan 1, 2016 and will be ended on December 31, 2040. Specially, the impact of inflammation and anti-inflammatory strategies on the early and late adverse events are investigated. Primary outcomes are severe systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), Sequential Organ Failure Assessment (SOFA) scores at 7 days following this current surgery. Secondary outcomes are SISR, 30-day mortality, operative mortality, hospital mortality, new-onset stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit.

Detailed description: Aortopathy represent a major clinical challenge and are regarded as one of the leading causes of mortality among cardiovascular disorders. However, the pathological mechanisms underlying aortopathy are still far from being well understood, which makes treating this life-threatening challenging. It is increasingly clear that inflammation plays a key role in the development and progression of acute aortic syndrome (AAS) independent of cholesterol and other traditional risk factors, and characterizes both systemic and local condition.

Currently, surgery is considered the best treatment option for patients with AAS. In addition to systemic inflammatory responses triggered by AAS itself, however, procedural factors including surgical trauma, anesthesia, cardiopulmonary bypass, hypothermia, circulatory arrest, and blood transfusion as well as mechanical ventilation initiated a cascade of inflammation, which further exacerbates "inflammatory storm", and is associated with significant postoperative mortality and morbidity. Along with surgical evolutions, scientists have made new discoveries and achievements in the underlying mechanism and understanding of inflammation of AAS, which greatly encourage us to optimize treatment for these patients. Going beyond traditional surgery, anti-inflammatory action is crucially important to target the residual cardiovascular risk by specific anti-inflammatory interventions as a crucially adjunct therapeutic strategy to improve the well-being of patient.

A better understanding of the interaction between patient's inflammatory responses and anti-inflammatory strategies which may limit the residual cardiovascular risk is essential for the development of novel preventive, diagnostic, and therapeutic approaches, providing a critical pathophysiological insight into the role of inflammation in risk assessment and anti-inflammatory targeting. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional surgical repair as well as basic therapy. Previous researches have shown that ulinastatin used in cardiac surgery may be effective in prevention of cardiovascular events through an anti-inflammatory effect. This residual inflammatory risk has increasingly become a viable therapeutic targeting on the background of validated surgical repair as well as basic medical therapy for AAS.

Although aortic dissection registries have been established during the last years, such as the International Registry of Acute Aortic Dissection (IRAD), the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) Registry, German Registry for Acute Aortic Dissection type A (GERAADA), the Society of Thoracic Surgeon (STS) database , and European Registry of Type A Aortic Dissection (ERTAAD), there are currently no dedicated registry to prospective collections and characteristics of inflammatory responses, anti-inflammatory strategies, and clinical outcomes especially for AAS patients. We have established a multicenter research collaboration (named "Chinese Registry of Additive Anti-inflammatory Action for Aortopathy \& Arteriopathy \[5A\]") and planned a prospectively observational study to understand the patient's inflammatory responses, characterize the potential anti-inflammatory strategies, and evaluate clinical outcome and prognosis of AAS patients at 15 years in a large study of Chinese population.

Eligibility criteria: Inclusion criteria

* Aged 18 years or older.
* Patients with diagnosis of AAS, including aortic dissection, penetrating aortic ulcer or intramural hematoma.
* Symptoms started within 14 days from surgery.
* Patients received medical therapy, open surgical, endovascular, or hybrid repair.
* Any other major cardiac surgical procedure concomitant with surgery for AAS, such as coronary artery bypass grafting or carotid artery replacement;
* The patient or guardian agrees to participate in this study. Exclusion criteria
* Patients aged \< 18 years.
* Onset of symptoms \> 14 days from surgery.
* AAS secondary to traumatic or iatrogenic injury.
* Patients who declined participation in registration and follow-up investigation.

Primary outcomes:
measure: Operative mortality
timeFrame: 30 days after treatment
measure: Severe systemic inflammatory response syndrome (SIRS)
timeFrame: 7 days after treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Fuwai Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Chongqing
country: China
facility: Chongqing Hospital of Jiangsu Provincial People's Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Suqian
country: China
facility: Suqian Hospital of of Nanjing Medical University
state: Jiangsu
city: Yangzhou
country: China
facility: Subei People's Hospital of Jiangsu Province
state: Jiangsu
city: Nanchang
country: China
facility: the Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Shanghai DeltaHealth Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Cardiovascular Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Kazak
country: China
facility: The Friendship Hospital of Yili Kazak Autonomous Prefecture
state: Xinjiang
city: Urumchi
country: China
facility: The Seventh Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: The First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Beijing
country: China
facility: Beijing Anzhen Hospital Capital Medical University
city: Beijing
country: China
facility: Beijing Chaoyang Hospital
city: Bengbu
country: China
facility: the First Affiliated Hospital of Bengbu Medical College
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Guilin
country: China
facility: the First Affiliated Hospital of Guilin Medical College
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
city: Nanjing
country: China
facility: Nanjing First Hospital, Nanjing Medical University
city: Qingdao
country: China
facility: the Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Shanghai East Hospital Tongji University
city: Shantou
country: China
facility: the First Affiliated Hospital of Shantou University Medical College
city: Tianjin
country: China
facility: Teda International Cardiovascular Hospital
city: Tianjin
country: China
facility: Tianjin Chest Hospital
city: Xiamen
country: China
facility: Xiamen Cardiovascular Hospital
Study officials:
affiliation: Beijing Anzhen Hospital
name: Hong-jia Zhang, MD
role: STUDY_DIRECTOR
affiliation: Nanjing Medical University
name: Hong Liu
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Anzhen Hospital
name: Si-chong Qian
role: PRINCIPAL_INVESTIGATOR
References: