The OPTIMA-5 Trail

NCT05023681 | Completed Phase 4

• 1 other identifier: 014
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 9

Brief Summary

This study was a prospective, multicenter, randomized, controlled, excellence clinical trial. Subjects meeting the inclusion/exclusion criteria were randomly assigned 1:1 to r-SAK group or the control group (normal saline). Emergency coronary angiography was performed and cardiac magnetic resonance imaging was performed 5 days after surgery, followed up to 30 days. At present, there is still a lack of clinical evidence on whether thrombolytic therapy is performed for acute ST-segment elevation myocardial infarction \<2 hours after the first medical contact and prime PCI. Compared to prime PCI, early thrombolytic therapy can undoubtedly shorten the implementation time of reperfusion strategy to the maximum. For highly effective thrombolytic drugs, it should also shorten the reperfusion time, reduce thrombotic load, possibly reduce the area of myocardial infarction and improve the prognosis of patients. In this study, normal saline was used as the control. To observe the efficacy of thrombolytic therapy with single intravenous infusion of recombinant glucokinase (r-SAK) at the first time in acute ST-segment elevation myocardial infarction. And the effect of r-SAK on improving myocardial tissue level perfusion, reducing myocardial infarction size, improving cardiac function and clinical prognosis in STEMI patients.

Conditions

Acute Myocardial Infarction

Keywords

Acute Myocardial Infarction；Recombinant Staphylokinase; thrombolysis

Outcome Measures

Primary Outcomes (2)

• the percentage of TIMI flow grade 2 and 3 or grade 3 after 60 minutes of the thrombolytic therapy

  The primary endpoint

  60 minutes

• the incidence of major bleeding defined as Bleeding Academic Research Consortium (BARC) ≥3 bleeding

  The main safety endpoint

  30 days

Secondary Outcomes (8)

• The percentage of TIMI flow grade 3 after PCI

  60 minutes

• Clinical net benefits of MACE and major bleeding events during hospitalization

  1 week

• MACCEs, defined as composite of all-cause death, myocardial infarction, unplanned revascularization, ischemic stroke and cardiogenic re-hospitalization recorded during 30-day follow-up

  30 days

• Infarct size, Microvascular obstruction, cardiac function (EF) and Intramuscular hemorrhageH detected by MRI 5 days after AMI

  5 days

• Major bleeding (BARC ≥3) and minor bleeding (BARC ≤2) events during 30-day follow-up

  30 days

Study Arms (2)

r-SAK treatment group

EXPERIMENTAL

intravenous injection of single bolus 5 mg r-SAK in 3min

Drug: Recombinant Staphylokinase

saline control group

PLACEBO COMPARATOR

intravenous injection of 10ml saline in 3min,r-SAK and saline are the same in appearance

Drug: normal saline

Interventions

Recombinant Staphylokinase DRUG

Intravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction

Also known as: r-SAK single intravenous injection for early treatment of acute myocardial infarction

r-SAK treatment group

normal saline DRUG

Intravenous injection of placebo(normal saline ) is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction

Also known as: normal saline intravenous injection for early treatment of acute myocardial infarction

saline control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18, ≦75 years old, weight ≥45kg, gender is not limited.
• Diagnosis of acute ST-segment elevation myocardial infarction (both of the following) (A) Ischemic chest pain lasting more than 30 minutes; (B) Ecg indicates ST-segment elevation ≥ 0.1mV in 2 or more limb leads, or ST-segment elevation ≥ 0.2mV in 2 or more adjacent chest leads;
• Time from onset of persistent ischemic chest pain to randomization ≤12 hours;
• Coronary angiography and/or PCI are expected to be performed within 2 hours of r-SAK thrombolysis.

You may not qualify if:

• Non-ST-segment elevation myocardial infarction;
• STEMI with cardiogenic shock;
• active bleeding or bleeding tendency, including Ⅲ, Ⅳ period history of retinopathy, retinal hemorrhage, gastrointestinal tract and urinary tract hemorrhage (1 month), ischemic stroke happened over the past 6 months, transient ischemic attack (TIA) happened over the past 6 weeks, hemorrhagic stroke in the past, unexplained platelet count \< 100 x 109 / L or Hemoglobin \<100g/L;
• Having a history of central nervous system trauma or known intracranial aneurysm;
• Recent (within 1 month) severe trauma, surgery or head injury;
• Suspected aortic dissection, infective endocarditis;
• Recent history of puncture which difficult hemostasis by compression (visceral biopsy, compartment puncture);
• Long-term use and/or current use of anticoagulant drugs;
• Hypertension not well controlled ≥180/110mmHg;
• Having severe hepatic and renal impairment (ALT, AST, γ-GT \> 2.5 times the upper limit of normal value; Cr \> 1.5 times upper normal);
• Known allergies to r-SAK;
• Pregnant, breastfeeding or planned pregnancy women and male patients with family planning;
• Patients who have participated in other clinical trials in the past 3 months;
• Having a history of myocardial infarction or CABG;
• Having taken antiplatelet drugs after pain onset, such as clopidogrel, prasugrel, cilostazol etc;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (9)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

Location

Changzhou Second People's Hospital

Changzhou, China

Location

The second Affiliated Hospital of Dalian Medical University

Dalian, China

Location

The Second Affiliated Hospital of Zhejiang University Medical College

Hangzhou, China

Location

Huai 'an Second People's Hospital affiliated to Nanjing Medical University

Huai'an, China

Location

Lianyungang First People's Hospital

Lianyungang, China

Location

Renji Hospital affiliated to Shanghai Jiaotong University

Shanghai, China

Location

Taizhou People's Hospital

Taizhou, China

Location

Affiliated Hospital of Jiangnan University

Wuxi, China

Location

Related Publications (16)

• Correction to: Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018 Mar 20;137(12):e493. doi: 10.1161/CIR.0000000000000573. No abstract available.

  PMID: 29555722 RESULT

• Heusch G, Libby P, Gersh B, Yellon D, Bohm M, Lopaschuk G, Opie L. Cardiovascular remodelling in coronary artery disease and heart failure. Lancet. 2014 May 31;383(9932):1933-43. doi: 10.1016/S0140-6736(14)60107-0. Epub 2014 May 13.

  PMID: 24831770 RESULT

• Agnoletti G, Cargnoni A, Agnoletti L, Di Marcello M, Balzarini P, Pasini E, Gitti G, Martina P, Ardesi R, Ferrari R. Experimental ischemic cardiomyopathy: insights into remodeling, physiological adaptation, and humoral response. Ann Clin Lab Sci. 2006 Summer;36(3):333-40.

  PMID: 16951276 RESULT

• Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J. 2016 Nov 7;37(42):3232-3245. doi: 10.1093/eurheartj/ehw334. Epub 2016 Aug 14. No abstract available.

  PMID: 27523477 RESULT

• Collen D, Lijnen HR. Thrombolytic agents. Thromb Haemost. 2005 Apr;93(4):627-30. doi: 10.1160/TH04-11-0724.

  PMID: 15841305 RESULT

• Pulicherla KK, Kumar A, Gadupudi GS, Kotra SR, Rao KR. In vitro characterization of a multifunctional staphylokinase variant with reduced reocclusion, produced from salt inducible E. coli GJ1158. Biomed Res Int. 2013;2013:297305. doi: 10.1155/2013/297305. Epub 2013 Aug 13.

  PMID: 23998121 RESULT

• Ueshima S, Matsuo O. Development of new fibrinolytic agents. Curr Pharm Des. 2006;12(7):849-57. doi: 10.2174/138161206776056065.

  PMID: 16515501 RESULT

• Yamamoto J, Kawano M, Hashimoto M, Sasaki Y, Yamashita T, Taka T, Watanabe S, Giddings JC. Adjuvant effect of antibodies against von Willebrand Factor, fibrinogen, and fibronectin on staphylokinase-induced thrombolysis as measured using mural thrombi formed in rat mesenteric venules. Thromb Res. 2000 Mar 1;97(5):327-33. doi: 10.1016/s0049-3848(99)00184-x.

  PMID: 10709908 RESULT

• Szemraj J, Stankiewicz A, Rozmyslowicz-Szerminska W, Mogielnicki A, Gromotowicz A, Buczko W, Oszajca K, Bartkowiak J, Chabielska E. A new recombinant thrombolytic and antithrombotic agent with higher fibrin affinity - a staphylokinase variant. An in-vivo study. Thromb Haemost. 2007 Jun;97(6):1037-45. doi: 10.1160/th06-10-0562.

  PMID: 17549308 RESULT

• Vakili B, Nezafat N, Negahdaripour M, Yari M, Zare B, Ghasemi Y. Staphylokinase Enzyme: An Overview of Structure, Function and Engineered Forms. Curr Pharm Biotechnol. 2017;18(13):1026-1037. doi: 10.2174/1389201019666180209121323.

  PMID: 29424308 RESULT

• Li CJ, Huang J, Yang ZJ, Cao KJ. Thrombolytic efficacy of native recombinant staphylokinase on femoral artery thrombus of rabbits. Acta Pharmacol Sin. 2007 Jan;28(1):58-65. doi: 10.1111/j.1745-7254.2007.00455.x.

  PMID: 17184583 RESULT

• Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.

  PMID: 21670242 RESULT

• Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Glob Heart. 2018 Dec;13(4):305-338. doi: 10.1016/j.gheart.2018.08.004. Epub 2018 Aug 25. No abstract available.

  PMID: 30154043 RESULT

• Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW; Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007 May 1;115(17):2344-51. doi: 10.1161/CIRCULATIONAHA.106.685313.

  PMID: 17470709 RESULT

• Halvorsen S, Storey RF, Rocca B, Sibbing D, Ten Berg J, Grove EL, Weiss TW, Collet JP, Andreotti F, Gulba DC, Lip GYH, Husted S, Vilahur G, Morais J, Verheugt FWA, Lanas A, Al-Shahi Salman R, Steg PG, Huber K; ESC Working Group on Thrombosis. Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: expert consensus paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J. 2017 May 14;38(19):1455-1462. doi: 10.1093/eurheartj/ehw454. No abstract available.

  PMID: 27789570 RESULT

• Chen P, Eikelboom JW, Tan C, Zhang W, Xu Y, Bai J, Wang J, Wang T, Gong X, Liu K, Chen X, Wang X, Zhu L, Zhao X, Yang N, Jiang J, Pu J, Zhao B, Chen Z, Li B, Wang G, Lu C, Ying L, Jiang M, Zhu X, Ma J, Dong Z, Li C, Zong J, Zhang F, Zhu J, Huang J, Kong X, Yu H, Li C; OPTIMA-5 Investigators. Single Bolus r-SAK Before Primary PCI for ST-Segment-Elevation Myocardial Infarction. Circ Cardiovasc Interv. 2024 Feb;17(2):e013455. doi: 10.1161/CIRCINTERVENTIONS.123.013455. Epub 2024 Jan 23.

  PMID: 38258563 DERIVED

Related Links

• Article Published in Chinese

MeSH Terms

Interventions

Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In this study, patients are randomly assigned 1:1 to the r-SAK treatment group and the saline control group using a central randomization system.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief leader of CCU

Study Record Dates

• First Submitted: August 22, 2021
• First Posted: August 26, 2021
• Study Start: October 29, 2021
• Primary Completion: August 14, 2022
• Study Completion: September 14, 2022
• Last Updated: January 13, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)