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
Red color represents old content. It may be empty showing addition in the new version.
Green color represents new content. It may be empty showing deletion in the new version.
Inline
Side by side
Added new contents,
deleted old contents,contents that are not changed.
New table contents
New table contents
Old table contents
Old table contents
Unchanged contents
Unchanged contents
Added new contents, contents that are not changed.
Deleted old contents, contents that are not changed.
Old table contents
Old table contents
Unchanged contents
Unchanged contents
New table contents
New table contents
Unchanged contents
Unchanged contents
Recruitment centers
#1
Name of recruitment center - English: Shohadaye Gomnam Hospital
Name of recruitment center - Persian: بیمارستان شهدای گمنام
Full name of responsible person - English: Dr.Mehdi Nazm deh
Full name of responsible person - Persian: دکتر مهدی نظم ده
Street address - English: Shahid Mohammad Reza Azam Nezami St., Khavaran St., Khorasan Sq., Tehran
Street address - Persian: تهران، میدان خراسان،خیابان خاوران، خیابان شهید محمدرضا اعظم نظامی
City - English: Tehran
City - Persian: تهران
Province: Tehran
Country: Iran (Islamic Republic of)
Postal code: 1794694616
Phone: +98 21 3631 2001
Fax:
Email: shgm-hospital@sbmu.ac.ir
Web page address: http://shgmc.sbmu.ac.ir/
Name of recruitment center - English: Shohadaye Gomnam Hospital Name of recruitment center - Persian: بیمارستان شهدای گمنام Full name of responsible person - English: Dr.Mehdi Nazm deh Full name of responsible person - Persian: دکتر مهدی نظم ده Street address - English: Shahid Mohammad Reza Azam Nezami St., Khavaran St., Khorasan Sq., Tehran Street address - Persian: تهران، میدان خراسان،خیابان خاوران، خیابان شهید محمدرضا اعظم نظامی City - English: Tehran City - Persian: تهران Province: Tehran Country: Iran (Islamic Republic of) Postal code: 1794694616 Phone: +98 21 3631 2001 Fax: Email: shgm-hospital@sbmu.ac.ir Web page address: http://shgmc.sbmu.ac.ir/
#2
Name of recruitment center - English: Zaeem Hospital
Name of recruitment center - Persian: بیمارستان زعیم
Full name of responsible person - English: Dr.Ghazaleh Hatami
Full name of responsible person - Persian: دکتر غزاله حاتمی
Street address - English: Zaeem Hospital, Sharif Abad, 35 kilometer to Imam Reza road
Street address - Persian: تهران - 35 کیلومتری جاده امام رضا (ع) خاوران بعد از پاکدشت ، اول شریف آباد بیمارستان زعیم
City - English: Tehran
City - Persian: Sharif Abad
Province: Tehran
Country: Iran (Islamic Republic of)
Postal code: 3394138861
Phone: +98 21 3347 2121
Fax:
Email: zaeemhospital@sbmu.ac.ir
Web page address: http://zpmc.sbmu.ac.ir/index.jsp?pageid=20585&p=1
Name of recruitment center - English: Zaeem Hospital Name of recruitment center - Persian: بیمارستان زعیم Full name of responsible person - English: Dr.Ghazaleh Hatami Full name of responsible person - Persian: دکتر غزاله حاتمی Street address - English: Zaeem Hospital, Sharif Abad, 35 kilometer to Imam Reza road Street address - Persian: تهران - 35 کیلومتری جاده امام رضا (ع) خاوران بعد از پاکدشت ، اول شریف آباد بیمارستان زعیم City - English: Tehran City - Persian: Sharif Abad Province: Tehran Country: Iran (Islamic Republic of) Postal code: 3394138861 Phone: +98 21 3347 2121 Fax: Email: zaeemhospital@sbmu.ac.ir Web page address: http://zpmc.sbmu.ac.ir/index.jsp?pageid=20585&p=1
Protocol summary
Study aim
To compare the Efficacy and Safety of Altelyse (bio-similar Alteplase) versus the brand Actilyse in Acute MI patients with ST elevation
Design
This is a randomized, double-blind , parallel groups, multi center, non-inferiority and phase III clinical trial sudy.
Settings and conduct
Study will be conducted in five hospitals in Tehran. They are Taleghani, Shohadaye-Tajrish, Loghman, Labafi-Nejad, and Fayazbakhsh hospitals.
Participants/Inclusion and exclusion criteria
Patients aged 18 years or older who have had an acute myocardial infarction with ST segment elevation and who either do not have access to Primary Percutaneous Cardiac Intervention (PPCI) or will take more than two hours to receive PPCI treatment, will be potentially eligible for this study. Patient should sign nformed consent form and should not have any contraindication for thrombolytic therapy.
Intervention groups
There are two intervention groups in this study. All patients in both groups will receive usual treatments including Aspirin, ADP antagonist, and anti-coagulant therapies. In group 1 thrombolytic therapy patients will receive thrombolytic therapy using Altelyse ( Alteplase made by Arena Hayat Danesh Co) and in group 2 patients will receive Actilyse (Alteplase made by boehringer-ingelheim). Thrombolytic therapy will be delivered by accelerated delivery including one bolus injection plus infusion over the next 1.5 hours.
Main outcome variables
Primary outcome in this study is ST resolution (STR) in 90 minutes. Secondary outcomes include complete or partial resolution of ST segment STR in 90 minutes, ST resolution in 180 minutes, all cause mortality in 30 days, cardiovascular mortality in 30 days, all cause in-hospital mortality, Ventricular Ejection Fraction (EF), bleeding following thrombolytic treatment, allergic drug reaction, and Major Adverse Cardiac Events (MACE)
General information
Reason for update
clinical trial site update and patient recruitment update
Acronym
ARENA
IRCT registration information
IRCT registration number:IRCT20190729044366N1
Registration date:2019-08-25, 1398/06/03
Registration timing:prospective
Last update:2021-10-03, 1400/07/11
Update count:2
Registration date
2019-08-25, 1398/06/03
Registrant information
Name
Babak Khoeini
Name of organization / entity
Arena Life Science Co
Country
Iran (Islamic Republic of)
Phone
+98 21 2242 3571
Email address
khoein.b@arenalifescience.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-06-22, 1400/04/01
Expected recruitment end date
2022-07-21, 1401/04/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
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
Public title
Comparing the safety and efficacy of Altelyse with Actilyse in acute myocardial infarction
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
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
Exclusion criteria:
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
Age
From 18 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data and Safety Monitoring Board
Sample size
Target sample size:
150
Randomization (investigator's opinion)
Randomized
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 (investigator's opinion)
Double blinded
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.
Placebo
Not used
Assignment
Parallel
Other design features
Acronym ARENA stands for Assessing Re-perfusion Efficacy in Nationally manufactured thrombolytic, Altelyse in AMI
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Shahid Beheshti University of Medical Science
Street address
Daneshjoo St., Velenjak
City
Tehran
Province
Tehran
Postal code
-
Approval date
2019-07-21, 1398/04/30
Ethics committee reference number
IR.SBMU.REC.1398.025
Health conditions studied
1
Description of health condition studied
Acute Myocardial Infarction with ST elevation
ICD-10 code
I21.3
ICD-10 code description
ST elevation (STEMI) myocardial infarction of unspecified site
Primary outcomes
1
Description
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.
Secondary outcomes
1
Description
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.
2
Description
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.
3
Description
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
4
Description
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
5
Description
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
6
Description
Ventricular Ejection Fraction
Timepoint
2 to 5 days following thrombolytic therapy
Method of measurement
Echocardiography
7
Description
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
8
Description
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.
9
Description
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)
Intervention groups
1
Description
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.
Category
Treatment - Drugs
2
Description
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.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
(Ayatollah) Taleghani Educational Hospital
Full name of responsible person
Dr Mohammad Piranfar
Street address
Tabnak St. Velenjak Region, Chamran High Way, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1985711151
Phone
+98 21 2243 2560
Fax
+98 21 2243 2570
Email
taleghanihospital@sbmu.ac.ir
Web page address
2
Recruitment center
Name of recruitment center
Loghman Hakim Hospital
Full name of responsible person
Dr. Mahdi Sheibani
Street address
Makhsoos St, South Karegar Ave, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1333631151
Phone
+98 21 5541 9005
Fax
+98 21 5541 7547
Email
loghman.hospital@sbmu.ac.ir
Web page address
https://lhmc.sbmu.ac.ir/
3
Recruitment center
Name of recruitment center
Shohadye Pakdasht Hospital
Full name of responsible person
Dr.Nahid Mohebi
Street address
Khatoon abad, Pakdasht,, Khavaran road 25 kilometer,Tehran Province
City
pakdasht
Province
Tehran
Postal code
1666663111
Phone
+98 21 3644 2012
Email
shpmc@sbmu.ac.ir
4
Recruitment center
Name of recruitment center
Shohadaye Tajrish Hospital
Full name of responsible person
Dr. Mahdi Pishgahi
Street address
Tajrish Sq., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1989934148
Phone
+98 21 2271 8000
Email
pr_shohada@sbmu.ac.ir
5
Recruitment center
Name of recruitment center
Shahid Fayyaz Bakhsh Hospital
Full name of responsible person
Dr. Mohsen Jamali
Street address
District 18, Tehran
City
Tehran
Province
Tehran
Postal code
1379613541
Phone
+98 21 6625 0645
Email
fayazbakhsh٦٧٣@gmail.com
Web page address
http://www.fayazhospital.com/
6
Recruitment center
Name of recruitment center
Shohadaye Gomnam Hospital
Full name of responsible person
Dr.Mehdi Nazm deh
Street address
Shahid Mohammad Reza Azam Nezami St., Khavaran St., Khorasan Sq., Tehran
City
Tehran
Province
Tehran
Postal code
1794694616
Phone
+98 21 3631 2001
Email
shgm-hospital@sbmu.ac.ir
Web page address
http://shgmc.sbmu.ac.ir/
7
Recruitment center
Name of recruitment center
Zaeem Hospital
Full name of responsible person
Dr.Ghazaleh Hatami
Street address
Zaeem Hospital, Sharif Abad, 35 kilometer to Imam Reza road
City
Tehran
Province
Tehran
Postal code
3394138861
Phone
+98 21 3347 2121
Email
zaeemhospital@sbmu.ac.ir
Web page address
http://zpmc.sbmu.ac.ir/index.jsp?pageid=20585&p=1
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Arena Life Science Company
Full name of responsible person
Dr. Babak Khoeeni
Street address
No 17, 2nd Golestan, Daneshjoo Blv. Velenjak
City
Tehran
Province
Tehran
Postal code
1984734351
Phone
+98 21 2680 2093
Email
khoein.b@arenalifescience.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Not applicable
Title and more details about the data/document
These includes identified individual participant data on primary and secondary outcomes, study protocol, informed consent form and clinical study report
When the data will become available and for how long
Data will be available one year after study completion or publication of the main results whichever comes later
To whom data/document is available
Data will only be available to academic researchers at the universities
Under which criteria data/document could be used
Data will only be shared for the purpose of meta-analysis
From where data/document is obtainable
You can contact Ms Hoda Shojaei at Arenalifesciences Co
What processes are involved for a request to access data/document
Medical Director of the Arenlifesciece co should make sure that the condition for sharing data is met and should approve it