Plasma Dipeptidyl-peptidase-4 Activities With No-reflow and Bleeding

Bleeding Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02849691
• Other study ID #: DPP4a-noreflow
• Status: Completed
• Phase: N/A
• First received: July 24, 2016
• Last updated: July 26, 2016
• Start date: January 2014

Study information

• Verified date: July 2016
• Source: Chinese PLA General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Observational

Clinical Trial Summary

Dipeptidyl-peptidase-4 (DPP4) is an important regulator of incretins and inflammation, and participates in the pathophysiological process of acute myocardial infarction (AMI). However clinical data of DPP4a in AMI patients is sparse. This study was to investigate the role of plasma DPP4 activity (DPP4a) in patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). This was a analysis of consecutive patients conducted at a tertiary referral center from January 2014 to October 2015. The investigators included 747 STEMI-patients, treated with PCI from January 2013 to October 2015. Blood samples were collected immediately at admission. The patients were divided into four groups according to DPP4a quartile.

Description:

ST-segment elevation myocardial infarction (STEMI) is an acute manifestation of coronary heart disease, remaining a frequent cause of death.A better understanding of risk factors and pathogenic mechanisms underlying STEMI may help improve the prognosis and life quality of these patients.Dipeptidyl peptidase 4 (DPP4) is an exopeptidase expressed on the surface of diverse cells, cleaving off amino-terminal dipeptides with either L-proline, L-alanine or serine at the penultimate position. As a cell surface protein, it participates in immune regulation, signal transduction and apoptosis. DPP4 also circulates as a soluble form in the plasma. Soluble DPP4 came from either membrane type clearance or secreted by cells like endothelial cells, with enzymatic activity. Plasma DPP4 activity (DPP4a) are elevated in several diseases, including type 2 diabetes, obesity, atherosclerosis and osteoporosis. Basic studies have showed that DPP4 inhibition leads improved survival and heart function after cardiac ischemia-reperfusion (I/R) injury, and this is partly due to activation of AKT (pAKT), pGSK3 and ANP pathways. Also inhibition of DPP4 can alleviate atherosclerosis and heart failure. Accordingly, one could hypothesize that high DPP4a may worsen myocardial I/R injury, causing poorer cardiovascular outcomes. However, no study has evaluated whether DPP4a is associated with adverse clinical outcomes in STEMI patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 747
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• a diagnosis of STEMI and needed PCI

Exclusion Criteria:

• patients with cancer

• patients who used DPP4 inhibitor

• patients who used GLP1 analogue

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Bleeding
• Dipeptidyl-peptidase-4
• Hemorrhage
• No-reflow
• PCI
• STEMI

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

References & Publications (5)

Connelly KA, Zhang Y, Advani A, Advani SL, Thai K, Yuen DA, Gilbert RE. DPP-4 inhibition attenuates cardiac dysfunction and adverse remodeling following myocardial infarction in rats with experimental diabetes. Cardiovasc Ther. 2013 Oct;31(5):259-67. doi: 10.1111/1755-5922.12005. — View Citation

Shigeta T, Aoyama M, Bando YK, Monji A, Mitsui T, Takatsu M, Cheng XW, Okumura T, Hirashiki A, Nagata K, Murohara T. Dipeptidyl peptidase-4 modulates left ventricular dysfunction in chronic heart failure via angiogenesis-dependent and -independent actions. Circulation. 2012 Oct 9;126(15):1838-51. doi: 10.1161/CIRCULATIONAHA.112.096479. Epub 2012 Oct 3. — View Citation

Windecker S, Bax JJ, Myat A, Stone GW, Marber MS. Future treatment strategies in ST-segment elevation myocardial infarction. Lancet. 2013 Aug 17;382(9892):644-57. doi: 10.1016/S0140-6736(13)61452-X. Review. — View Citation

Zhong J, Maiseyeu A, Davis SN, Rajagopalan S. DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition. Circ Res. 2015 Apr 10;116(8):1491-504. doi: 10.1161/CIRCRESAHA.116.305665. Review. — View Citation

Zhong J, Rajagopalan S. Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease. Front Immunol. 2015 Sep 25;6:477. doi: 10.3389/fimmu.2015.00477. eCollection 2015. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	a change in the prevalence of no-reflow	TIMI flow grade of <3 with a myocardial blush grade of 0-1 was defined as angiographic no-reflow	immediately after PCI	No
Secondary	in-hospital major adverse cardiac or cerebrovascular events	the composite of death, nonfatal MI, or stroke	up to 2 week after PCI (until discharge)	No
Secondary	in-hospital complications	defined as acute heart failure, atrial fibrillation, chest pain or re-acute myocardial infarction, complete atrioventricular block, cerebrovascular disease, ventricular fibrillation or ventricular tachycardia	up to 2 week after PCI (until discharge)	No
Secondary	in-hospital major bleeding	defined as absolute hemoglobin drop (baseline to nadir)=4g/dl, intracranial hemorrhage, retroperitoneal hemorrhage, use of red blood cell transfusion in patients with a baseline hemoglobin =9.0 g/dl, and use of red blood cell transfusion among patients with a baseline hemoglobin <9.0 g/dl and a witnessed bleeding event	up to 2 week after PCI (until discharge)	No