Prolonged Clinical Follow-up of OPTIMA-5

NCT05649696 | Completed Phase 4 DMC

• 1 other identifier: 020
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 8

Brief Summary

The OPTIMA-5 trial is a prospective, multi-center, randomized, patient blinded, controlled trial comparing a single bolus of half-dose recombinant staphylokinase (r-SAK) with normal saline (NS) in patients with ST-segment elevation myocardial infarction (STEMI) presenting ≤12 hours of symptom onset and expected to undergo primary percutaneous coronary intervention (PPCI) within 120 minutes. The results of OPTIMA-5 showed that a single bolus r-SAK prior to PPCI for STEMI improves infarct related artery (IRA) patency and reduces infarct size without increasing major bleeding. On this basis, this study was designed to investigate the effect of the novel reperfusion strategy on 1-year outcomes of patients with STEMI.

Conditions

ST-segment Elevation Myocardial Infarction (STEMI)

Keywords

ST Elevation Myocardial Infarction; Recombinant Staphylokinase

Outcome Measures

Primary Outcomes (1)

• MACE

  A composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia

  Within 360 days

Secondary Outcomes (1)

• Adverse cardiac and cerebrovascular events

  Within 360 days

Other Outcomes (3)

• r-SAK antibody level in human serum

  Day 90 ± 7, Day 180 ± 7, Day 360 ± 14

• In-vitro thrombolysis rate

  60 minutes after In-vitro thrombolysis

• r-SAK activity before and after in-vitro thrombolysis

  Immediately before in-vitro thrombolysis and 60 minutes after In-vitro thrombolysis

Study Arms (3)

r-SAK group

EXPERIMENTAL

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

Drug: Recombinant Staphylokinase

normal saline group

PLACEBO COMPARATOR

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

Drug: Normal Saline

patients with coronary artery disease

NO INTERVENTION

20 ml arterial blood samples and 5 ml venous blood samples were collected from patients before coronary angiography

Interventions

Recombinant Staphylokinase DRUG

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

r-SAK group

Normal Saline DRUG

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

normal saline group

Eligibility Criteria

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

You may not qualify if:

• Age 18-75 years, weight ≥45 kg;
• Diagnosed as STEMI (meeting the following two criteria simultaneously):
• i. Ischemic chest pain lasts ≥30 minutes; ii. Electrocardiogram indicates that ST-segment elevation ≥2 mm in 2 or more contiguous precordial leads or ≥1 mm in 2 or more peripheral leads;
• Time from onset of persistent chest pain to randomization \<12 hours;
• Primary PCI expected to be performed within 120 minutes.
• Cardiogenic shock;
• Active bleeding or at high risk of bleeding (including grade Ⅲ or Ⅳ retinopathy or retinal gastrointestinal or urinary tract hemorrhage within the past 1 month);
• Ischemic stroke or TIA in the past 6 months;
• History of hemorrhagic stroke;
• Platelet count \<100×109/L or hemoglobin \<100 g/L;
• Known intracranial aneurysm;
• Severe trauma, surgery or head injury within 1 month;
• Suspected aortic dissection or infective endocarditis;
• Recent puncture with difficult hemostasis by compression (eg, visceral biopsy, compartment puncture);
• Currently taking anticoagulants;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (8)

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

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

Huai'an, China

Location

Lianyungang First People's Hospital

Lianyungang, China

Location

Taizhou People's Hospital

Taizhou, China

Location

Affiliated Hospital of Jiangnan University

Wuxi, China

Location

The Second Affiliated Hospital of Zhejiang University Medical College

Zhejiang, China

Location

Related Publications (15)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

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

  PMID: 15841305 BACKGROUND

• 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 BACKGROUND

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

  PMID: 16515501 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

Related Links

• OPTIMA-5

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Cardiology

Study Record Dates

• First Submitted: November 24, 2022
• First Posted: December 14, 2022
• Study Start: October 29, 2021
• Primary Completion: September 14, 2023
• Study Completion: October 1, 2023
• Last Updated: September 25, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (8)