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IRCT20190729044366N1 IRCT 2019-08-25 Arena Life Science Company Comparing the safety and efficacy of Altelyse with Actilyse in acute myocardial infarction ARENA A randomized, double-blind , parallel groups, multi center, non-inferiority and phase III clinical trial to compare the Efficacy and Safety of Altelyse (bio-similar Alteplase) versus the brand Actilyse in Acute MI patients with ST elevation 2021-06-22 anticipated 150 Complete https://irct.ir/trial/41354 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Other design features: Acronym ARENA stands for Assessing Re-perfusion Efficacy in Nationally manufactured thrombolytic, Altelyse in AMI, Randomization description: We used block randomization stratified by hospitals using variable block size of 4 and 6. A separate chain of randomization sequence will be developed for each hospital. Excel software and rand() function will be used to create the random sequences. Concealment will be carried out and a random code will be assigned to every patient according to the randomization sequence. The codes will be put in sealed envelops and the envelops will be numbered incrementally from 1 according to the randomization sequence. For each eligible patient enrolled to the study an envelop will be opened according to the sequential number. Patients will receive the intervention assigned to them based on the code inside the envelop, Blinding description: In this study we used secondary packaging of Actilyse and Altlelyse to achieve blinding. The packages will be labelled using the concealment codes. Once the randomization is done, and the thrombolytic treatment package for the patient is known, a separate nurse not in the study team, will be given the responsibility to open the package and prepare the thrombolytic injection. It will then be given to the research team for use. 3 Acute Myocardial Infarction with ST elevation. Intervention 1: Intervention group 1: This group will receive thrombolytic therapy using Altelyse ( Alteplase made by Arena Hayat Danesh Co). People weighing more than 67kg will receive 15 mg bolus, 50 mg in the first 30 minutes and 35 mg within the next 60 minutes. People weighing 67kg or less will receive 15 mg bolus, 0.75 mg/kg in the first 30 minutes and 0.5 mg/kg within the next 60 minutes. All patients in the intervention groups 1 and 2 will receive Aspirin, ADP receptor antagonists and Anticoagulant therapy. Aspirin therapy: All patients who are not on Aspirin will receive 300-325 mg Aspirin in the emergency room. ADP receptor antagonist therapy: People not on clopidogrel and 75 years old or less will receive 300 mg clopidogrel loading dose and then 75mg daily. People not on clopidogrel and older than 75 years will only receive the daily dose without the loading dose. Anticoagulant therapy: All patients will receive one bolus injection of Unfractionated heparin 60 unit per kg (maximum 4000 units) followed by 12u/kg (maximum 1000 units) per hour until PTT reaches to 1.5 to 2 times normal (50-70 seconds) and stays at that level. Beta blockers, Angiotensin Enzyme inhibitors (ACE/ARB receptor inhibitors/blockers) and Statins will be given according to the existing guidelines. Intervention 2: Intervention group 2: This group will receive thrombolytic therapy using Actilyse. People weighing more than 67kg will receive 15 mg bolus, 50 mg in the first 30 minutes and 35 mg within the next 60 minutes. People weighing 67kg or less will receive 15 mg bolus, 0.75 mg/kg in the first 30 minutes and 0.5 mg/kg within the next 60 minutes. All patients in the intervention groups 1 and 2 will receive Aspirin, ADP receptor antagonists and Anticoagulant therapy. Aspirin therapy: All patients who are not on Aspirin will receive 300-325 mg Aspirin in the emergency room. ADP receptor antagonist therapy: People not on clopidogrel and 75 years old or less will receive 300 mg clopidogrel loading dose and then 75mg daily. People not on clopidogrel and older than 75 years will only receive the daily dose without the loading dose. Anticoagulant therapy: All patients will receive one bolus injection of Unfractionated heparin 60 unit per kg (maximum 4000 units) followed by 12u/kg (maximum 1000 units) per hour until PTT reaches to 1.5 to 2 times normal (50-70 seconds) and stays at that level. Beta blockers, Angiotensin Enzyme inhibitors (ACE/ARB receptor inhibitors/blockers) and Statins will be given according to the existing guidelines. Yes - There is a plan to make this available What will be shared: These includes identified individual participant data on primary and secondary outcomes, study protocol, informed consent form and clinical study report When: Data will be available one year after study completion or publication of the main results whichever comes later To whom: Data will only be available to academic researchers at the universities Conditions: Data will only be shared for the purpose of meta-analysis Where to obtain: You can contact Ms Hoda Shojaei at Arenalifesciences Co How to obtain: Medical Director of the Arenlifesciece co should make sure that the condition for sharing data is met and should approve it Comments: none
public Hoda Flah Shojaee
No 17, 2nd Golestan, Daneshjoo BLV, Velenjak
Tehran Iran (Islamic Republic of) 1984734351 +98 21 2680 2093 shojaee.h@arenalifescience.com Arena Life Science Co. scientific Dr.Mohammadreza Beyranvand
Tehran, Velenjak، 7th Floor, Bldg No.2 SBUMS, Arabi Ave
Tehran Iran (Islamic Republic of) 1985717443 +98 912 134 8366 beyran4@yahoo.com Shahid Beheshti University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Chest pain compatible with ischemic heart disease for more than 20 minutes Start of symptoms of Acute Myocardial Infarction (Peak of chest pain) 12 hours (Maximum) before thrombolytic treatment Signs of Acute Myocardial Infarction in Electrocardiogram: ST elevation of 0.1 mili-volt or more in two adjacent leads other than v2 and v3; ST elevation of 0.25 mili-volt or more in v2 and v3 leads in men younger than 40 years; ST elevation of 0.2 mili-volt or more in v2 and v3 leads in men older than 40 years; ST elevation of 0.15 mili-volt or more in v2 and v3 leads in women irrespective of their age. Lack of access to cath lab to do PPI, Primary Per-cutaneous Coronary Intervention or expecting a delay more than 2 hours between between first medical contact and performance of first balloon dilatation excluding the time takes from first medical contact till the start of thrombolytic therapy. Signed informed consent Age of 18 years or more 18 years no limit Both Presence of left bundle block in electrocardiogram Presence of accompanying severe diseases such as renal failure (GFR<30); hepatic failure; POrtal hypertension; Hepatitis; Thrombocytopaenia; Known pancreatitis (information gathered from first clinical examination upon arrival because of cheat pain Cardiogenic shock (Systolic pressure less than 90 mm Hg) Killip class III & IV Any history of intracranial bleeding or stroke with unknown origin irrespective of the time of occurrence Ischemic stroke Known central nervous system lesions, neoplasms (primary or metastatic), arteriovenous malformations Aortic dissection Active bleeding or known bleeding disorder (excluding menses) Major trauma to Head and Neck in the last 3 months Intracranial or spinal surgery in the last 2 months Other major trauma or surgery within the preceding month Gastrointestinal bleeding within the preceding month Sever uncontrolled hypertension (Resistant to emergency treatment) Non-compressible punctures in the past 24 hours (e.g. liver biopsy, lumbar puncture) History of poorly controlled chronic hypertension Hypertension at the time of eligibility assessment: Systolic BP >180 mm Hg or diastolic BP > 110 mm Hg Transient ischemic attack in the preceding 6 months Dementia Pregnancy or within 1 week postpartum Internal bleeding within the last 2-4 weeks Active peptic ulcer Infectious endocarditis Cardiopulmonary resuscitation that has caused injury to the chest or lasted more than 10 minutes Patients who receive anticoagulant therapy such as warfarin Advanced liver disease Known intracranial lesions other than those listed as absolute contraindications for thrombolytic therapy Diabetic Hemorrhagic Retinopathy or other hemorrhagic ophthalmic conditions I21.3 ST elevation (STEMI) myocardial infarction of unspecified site Treatment - Drugs Treatment - Drugs Intervention group 1: This group will receive thrombolytic therapy using Altelyse ( Alteplase made by Arena Hayat Danesh Co). People weighing more than 67kg will receive 15 mg bolus, 50 mg in the first 30 minutes and 35 mg within the next 60 minutes. People weighing 67kg or less will receive 15 mg bolus, 0.75 mg/kg in the first 30 minutes and 0.5 mg/kg within the next 60 minutes. All patients in the intervention groups 1 and 2 will receive Aspirin, ADP receptor antagonists and Anticoagulant therapy. Aspirin therapy: All patients who are not on Aspirin will receive 300-325 mg Aspirin in the emergency room. ADP receptor antagonist therapy: People not on clopidogrel and 75 years old or less will receive 300 mg clopidogrel loading dose and then 75mg daily. People not on clopidogrel and older than 75 years will only receive the daily dose without the loading dose. Anticoagulant therapy: All patients will receive one bolus injection of Unfractionated heparin 60 unit per kg (maximum 4000 units) followed by 12u/kg (maximum 1000 units) per hour until PTT reaches to 1.5 to 2 times normal (50-70 seconds) and stays at that level. Beta blockers, Angiotensin Enzyme inhibitors (ACE/ARB receptor inhibitors/blockers) and Statins will be given according to the existing guidelines. Intervention group 2: This group will receive thrombolytic therapy using Actilyse. People weighing more than 67kg will receive 15 mg bolus, 50 mg in the first 30 minutes and 35 mg within the next 60 minutes. People weighing 67kg or less will receive 15 mg bolus, 0.75 mg/kg in the first 30 minutes and 0.5 mg/kg within the next 60 minutes. All patients in the intervention groups 1 and 2 will receive Aspirin, ADP receptor antagonists and Anticoagulant therapy. Aspirin therapy: All patients who are not on Aspirin will receive 300-325 mg Aspirin in the emergency room. ADP receptor antagonist therapy: People not on clopidogrel and 75 years old or less will receive 300 mg clopidogrel loading dose and then 75mg daily. People not on clopidogrel and older than 75 years will only receive the daily dose without the loading dose. Anticoagulant therapy: All patients will receive one bolus injection of Unfractionated heparin 60 unit per kg (maximum 4000 units) followed by 12u/kg (maximum 1000 units) per hour until PTT reaches to 1.5 to 2 times normal (50-70 seconds) and stays at that level. Beta blockers, Angiotensin Enzyme inhibitors (ACE/ARB receptor inhibitors/blockers) and Statins will be given according to the existing guidelines. Percentage of ST resolution (STR) at 90 minutes. Timepoint: 90 minutes after start of thrombolytic therapy. Method of measurement: To estimate percentage of ST resolution at 90 minutes, we will measure the height of ST elevation at 20 milisecond after J point in those leads that have shown elevation of ST in a 12 lead standard ECG at time points 0 and 90. Sum of ST elevations in all 12 leads at 90 minutes will be deducted from the sum of ST elevations at time 0 to work out the total ST resolution (STR) at 90 minutes. We will then calculate the percentage of ST resolution by dividing total STR at 90 minutes to the sum of ST elevations at time 0. In a second measurement approach, percentage of patients who have had more than 50% resolution in their ECG lead with highest ST elevation will be calculated. Complete or partial resolution of ST segment (STR) in 90 minutes. Timepoint: 90 Minutes after thrombolytic therapy. Method of measurement: Complete resolution is defined as 70% resolution in sum of ST elevations and partial resolution is defined as 30 to 70% resolution in sum of ST elevations. Method of calculation of STR is the same as the primary outcome. Percentage of ST resolution (STR) at 180 minutes. Timepoint: 180 Minutes after thrombolytic therapy. Method of measurement: To estimate percentage of ST resolution at 180 minutes, we will measure the height of ST elevation at 20 milisecond after J point in those leads that have shown elevation of ST in a 12 lead standard ECG at time points 0 and 180. Sum of ST elevations in all 12 leads at 180 minutes will be deducted from the sum of ST elevations at time 0 to work out the total ST resolution (STR) at 180 minutes. We will then calculate the percentage of ST resolution by dividing total STR at 180 minutes to the sum of ST elevations at time 0. All cause mortality in 30 days. Timepoint: 30 days after intervention. Method of measurement: All deaths irrespective of the cause of death in the first 30 days following thrombolytic therapy starting from the First Medical Contact (FMC) will be counted. Cardiovascular mortality in 30 days. Timepoint: 30 days after intervention. Method of measurement: All cardiovascular deaths in the first 30 days following thrombolytic therapy starting from the First Medical Contact (FMC) will be counted. In-hospital mortality due to any cause. Timepoint: Up until discharge from hospital. Method of measurement: All deaths irrespective of their cause up until discharge from hospital will be counted. Ventricular Ejection Fraction. Timepoint: 2 to 5 days following thrombolytic therapy. Method of measurement: Echocardiography. Bleeding. Timepoint: After thrombolytic therapy. Method of measurement: All episodes of major and minor bleeding following thrombolytic therapy will be recorded and categorized in three groups according to GUSTO 5 criteria. Severe or life threatening bleeding: Intracranial bleeding and any other bleeding that cause severe haemodynamic instability for the patient. Moderate bleeding: patient will need blood transfusion. Mild bleeding: all other bleeding. Allergic drug reaction. Timepoint: After thrombolytic therapy. Method of measurement: Allergic skin reactions at the injection site and systemic reactions including anaphylactic shock, Angioedema, Urticaria, and drop in systolic blood pressure to 90 mmHg or lower, will be identified and recorded. MACE (Major Adverse Cardiac Events). Timepoint: After thrombolytic therapy. Method of measurement: Any of the following adverse cardiac events will be counted: Death, Bleeding GUSTO type I and II, Cerebrovascular Accident (CVA). Arena Life Science Company Approved 2019-07-21 Shahid Beheshti University of Medical Science Daneshjoo St., Velenjak Tehran Tehran Iran (Islamic Republic of)