Evaluating the safety of Administration of Adenosine, Lidocaine, and Mg(ALM) cocktail among Multiple Trauma Patients receiving Massive Transfusion with dose escalation A phase I, clinical trial
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General information
Due to the fact that the patients in the recovery room of the hospital usually receive up to 2 packs of blood and if needed, the rest of the blood is done in the inpatient departments or after transfer for better monitoring of the patients in the recovery room the criteria for inclusion in the study was changed instead of starting from the third pack to the second pack. Also, due to the lack of hypertonic saline, 3% of normal saline will be used in the blous dose.
Also, due to the fact that people aged 16 to 18 are also considered as adult patients in the field of trauma, and due to the high prevalence of trauma incidents requiring transfusion in these people, they can benefit from this study. The minimum age for entering the study is 18 years. changed to 16 years.
Also, considering the priority of investigating the effect of the cocktail on trauma patients receiving blood, and considering that most of the time such patients do not experience a severe drop in blood pressure or an increase in heart rate, and their injury severity criterion score is not necessarily more than 16; The condition of blood pressure below 70 or blood pressure below 90 with a heart rate of more than 108 was removed to enter the study, and the focus will be on patients receiving the second pack and beyond, regardless of pressure or heart rate. Also, the condition of injury severity criterion score of more than 16 to enter the study will be removed.
Due to the fact that the patients in the recovery room of the hospital usually receive up to 2 packs of blood and if needed, the rest of the blood is done in the inpatient departments or after transfer for better monitoring of the patients in the recovery room the criteria for inclusion in the study was changed instead of starting from the third pack to the second pack. Also, due to the lack of hypertonic saline, 3% of normal saline will be used in the blous dose.
Also, due to the fact that people aged 16 to 18 are also considered as adult patients in the field of trauma, and due to the high prevalence of trauma incidents requiring transfusion in these people, they can benefit from this study. The minimum age for entering the study is 18 years. changed to 16 years.
Also, considering the priority of investigating the effect of the cocktail on trauma patients receiving blood, and considering that most of the time such patients do not experience a severe drop in blood pressure or an increase in heart rate, and their injury severity criterion score is not necessarily more than 16; The condition of blood pressure below 70 or blood pressure below 90 with a heart rate of more than 108 was removed to enter the study, and the focus will be on patients receiving the second pack and beyond, regardless of pressure or heart rate. Also, the condition of injury severity criterion score of more than 16 to enter the study will be removed.
Many critically ill patients with low blood pressure and heavy bleeding are transferred to the operating room after receiving a blood bag and receive subsequent blood bags in the operating room. These patients also benefit from this study, so patients with a systolic pressure below 80 who receive the first blood bag are also added to the conditions of entering the study
Due to the fact that the patients in the recovery room of the hospital usually receive up to 2 packs of blood and if needed, the rest of the blood is done in the inpatient departments or after transfer for better monitoring of the patients in the recovery room the criteria for inclusion in the study was changed instead of starting from the third pack to the second pack. Also, due to the lack of hypertonic saline, 3% of normal saline will be used in the blous dose. Also, due to the fact that people aged 16 to 18 are also considered as adult patients in the field of trauma, and due to the high prevalence of trauma incidents requiring transfusion in these people, they can benefit from this study. The minimum age for entering the study is 18 years. changed to 16 years. Also, considering the priority of investigating the effect of the cocktail on trauma patients receiving blood, and considering that most of the time such patients do not experience a severe drop in blood pressure or an increase in heart rate, and their injury severity criterion score is not necessarily more than 16; The condition of blood pressure below 70 or blood pressure below 90 with a heart rate of more than 108 was removed to enter the study, and the focus will be on patients receiving the second pack and beyond, regardless of pressure or heart rate. Also, the condition of injury severity criterion score of more than 16 to enter the study will be removed. Many critically ill patients with low blood pressure and heavy bleeding are transferred to the operating room after receiving a blood bag and receive subsequent blood bags in the operating room. These patients also benefit from this study, so patients with a systolic pressure below 80 who receive the first blood bag are also added to the conditions of entering the study
به دلیل این که بیماران اتاق احیای بیمارستان معمولا تا ۲ پک خون دریافت می کنند و در صورت نیاز بقیه خون در بخش های بستری یا پس از ترانسفر انجام می شود برای تحت نظر بودن بهتر بیماران در اتاق احیا مطالعه به جای شروع از سومین پک به دومین پک تغییر داده شد همینطور در دوز بلوس به دلیل نبود سالین هایپر تونیک ۳درصد از نرمال سالین استفاده خواهد شد
همینطور به علت این که افراد ۱۶ تا ۱۸ سال هم عضو بیماران بزرگسال حیطه تروما به حساب می آیند و به دلیل شیوع بالای حوادث تروما با نیاز به ترنسفوژن در این افراد می توانند از این مطالعه سود ببرند حد پایین سن ورود به مطالعه از ۱۸ سال به ۱۶ سال تغییر پیدا کرد
همینطور با توجه به اولویت بررسی تاثیر کوکتل بر بیماران ترومایی دریافت کننده خون و با توجه به اینکه در اکثر مواقع این گونه بیماران با افت شدید فشار خون یا افزایش ضربان قلب مواجه نمیشوند و لزوماً نمره معیار شدت جراحت برای آنها بیش از ۱۶ نمیباشد؛ شرط فشار زیر ۷۰ یا فشار زیر ۹۰ همراه با ضربان قلب بیش از ۱۰۸ برای ورود به مطالعه حذف شد و تمرکز روی بیماران دریافت کننده پک دوم به بعد خواهد بود صرف نظر از فشار یا ضربان قلب. همینطور شرط نمره معیار شدت جراحت بیش از ۱۶ برای ورود به مطالعه حذف خواهد شد.
به دلیل این که بیماران اتاق احیای بیمارستان معمولا تا ۲ پک خون دریافت می کنند و در صورت نیاز بقیه خون در بخش های بستری یا پس از ترانسفر انجام می شود برای تحت نظر بودن بهتر بیماران در اتاق احیا مطالعه به جای شروع از سومین پک به دومین پک تغییر داده شد همینطور در دوز بلوس به دلیل نبود سالین هایپر تونیک ۳درصد از نرمال سالین استفاده خواهد شد
همینطور به علت این که افراد ۱۶ تا ۱۸ سال هم عضو بیماران بزرگسال حیطه تروما به حساب می آیند و به دلیل شیوع بالای حوادث تروما با نیاز به ترنسفوژن در این افراد می توانند از این مطالعه سود ببرند حد پایین سن ورود به مطالعه از ۱۸ سال به ۱۶ سال تغییر پیدا کرد
همینطور با توجه به اولویت بررسی تاثیر کوکتل بر بیماران ترومایی دریافت کننده خون و با توجه به اینکه در اکثر مواقع این گونه بیماران با افت شدید فشار خون یا افزایش ضربان قلب مواجه نمیشوند و لزوماً نمره معیار شدت جراحت برای آنها بیش از ۱۶ نمیباشد؛ شرط فشار زیر ۷۰ یا فشار زیر ۹۰ همراه با ضربان قلب بیش از ۱۰۸ برای ورود به مطالعه حذف شد و تمرکز روی بیماران دریافت کننده پک دوم به بعد خواهد بود صرف نظر از فشار یا ضربان قلب. همینطور شرط نمره معیار شدت جراحت بیش از ۱۶ برای ورود به مطالعه حذف خواهد شد.
بسیاری از بیماران بدحال با فشار پایین و خونریزی شدید پس از دریافت یک کیسه خون به اتاق عمل منتقل میشوند و کیسههای بعدی خون را در اتاق عمل دریافت میکنند این بیماران نیز از این مطالعه سود میبرند بنابراین به شروط ورود به مطالعه بیماران با فشار سیستول زیر ۸۰ که اولین بگ خون را دریافت میکنند نیز اضافه شد
به دلیل این که بیماران اتاق احیای بیمارستان معمولا تا ۲ پک خون دریافت می کنند و در صورت نیاز بقیه خون در بخش های بستری یا پس از ترانسفر انجام می شود برای تحت نظر بودن بهتر بیماران در اتاق احیا مطالعه به جای شروع از سومین پک به دومین پک تغییر داده شد همینطور در دوز بلوس به دلیل نبود سالین هایپر تونیک ۳درصد از نرمال سالین استفاده خواهد شد همینطور به علت این که افراد ۱۶ تا ۱۸ سال هم عضو بیماران بزرگسال حیطه تروما به حساب می آیند و به دلیل شیوع بالای حوادث تروما با نیاز به ترنسفوژن در این افراد می توانند از این مطالعه سود ببرند حد پایین سن ورود به مطالعه از ۱۸ سال به ۱۶ سال تغییر پیدا کرد همینطور با توجه به اولویت بررسی تاثیر کوکتل بر بیماران ترومایی دریافت کننده خون و با توجه به اینکه در اکثر مواقع این گونه بیماران با افت شدید فشار خون یا افزایش ضربان قلب مواجه نمیشوند و لزوماً نمره معیار شدت جراحت برای آنها بیش از ۱۶ نمیباشد؛ شرط فشار زیر ۷۰ یا فشار زیر ۹۰ همراه با ضربان قلب بیش از ۱۰۸ برای ورود به مطالعه حذف شد و تمرکز روی بیماران دریافت کننده پک دوم به بعد خواهد بود صرف نظر از فشار یا ضربان قلب. همینطور شرط نمره معیار شدت جراحت بیش از ۱۶ برای ورود به مطالعه حذف خواهد شد. بسیاری از بیماران بدحال با فشار پایین و خونریزی شدید پس از دریافت یک کیسه خون به اتاق عمل منتقل میشوند و کیسههای بعدی خون را در اتاق عمل دریافت میکنند این بیماران نیز از این مطالعه سود میبرند بنابراین به شروط ورود به مطالعه بیماران با فشار سیستول زیر ۸۰ که اولین بگ خون را دریافت میکنند نیز اضافه شد
Candidate to recieve the second pack of packed red blood cell
Candidate to recieve the second pack of packed red blood cell
A candidate to receive the first bag of red blood cells who has a systolic pressure of 80 or lower
Candidate to recieve the second pack of packed red blood cell A candidate to receive the first bag of red blood cells who has a systolic pressure of 80 or lower
کاندیدای دریافت کیسه دوم گلبول قرمز فشرده
کاندیدای دریافت کیسه دوم گلبول قرمز فشرده
کاندیدای دریافت اولین کیسه گلبول قرمز که فشار سیستول ۸۰ یا پایینتر دارد
کاندیدای دریافت کیسه دوم گلبول قرمز فشرده کاندیدای دریافت اولین کیسه گلبول قرمز که فشار سیستول ۸۰ یا پایینتر دارد
Protocol summary
Study aim
Determining the safety of Administration of Adenosine, Lidocaine, and Mg++(ALM) cocktail among Multiple Trauma Patients receiving Massive Transfusion and Admitted to the Resuscitation Room of Shahid Rajaee Trauma Hospital in Shiraz
Design
a single-center, phase 1 trial , on 17 paitients, without control group
Settings and conduct
Eligible patients who transferred from the scene of trauma to resuscitation room will be treated with cocktail.
Participants/Inclusion and exclusion criteria
Eligible patients are between the ages of 16 and 60 who were transferred directly from the scene to the resuscitation room of Shahid Rajaei Trauma Hospital in Shiraz. Inclusion criteria will include patients who are candidates to receive a second bag of packed red blood cells. the paitients with severe underlying diseases (specially severe cardiac and pulmonary diseases and renal failure) ,and those who experienced slash thoracotomy, or if they have penetrating Traumatic brain injury or exposed brain matter. Also paitients with an irregular base ECG will be excluded from trial
Intervention groups
The cocktail will be started in a group of 4 patients. if safety is confirmed the dose will be increased in next three patients.The ALM combination will be administered as the bolus and maintenance IV fluid. The maximom bolus dose of ALM IV injection consists of 200cc of normal saline,(87mg) of 2% Lidocaine, (6 mg) of adenosine and (30mg) of magnesium sulfate .The maximum dose of drip combination consists of 0.16 mg/kg/hr lidocaine, 0.19 mg/kg/hr Adenosine, and 0.2 mg/kg/hr MgSO4.Every drip component should be injected from separate bottle in 300 cc normal saline .
Main outcome variables
side effects;reduction in mortality ,hospitalizatin time ,amount of pack cell recieved
General information
Reason for update
Due to the fact that the patients in the recovery room of the hospital usually receive up to 2 packs of blood and if needed, the rest of the blood is done in the inpatient departments or after transfer for better monitoring of the patients in the recovery room the criteria for inclusion in the study was changed instead of starting from the third pack to the second pack. Also, due to the lack of hypertonic saline, 3% of normal saline will be used in the blous dose.
Also, due to the fact that people aged 16 to 18 are also considered as adult patients in the field of trauma, and due to the high prevalence of trauma incidents requiring transfusion in these people, they can benefit from this study. The minimum age for entering the study is 18 years. changed to 16 years.
Also, considering the priority of investigating the effect of the cocktail on trauma patients receiving blood, and considering that most of the time such patients do not experience a severe drop in blood pressure or an increase in heart rate, and their injury severity criterion score is not necessarily more than 16; The condition of blood pressure below 70 or blood pressure below 90 with a heart rate of more than 108 was removed to enter the study, and the focus will be on patients receiving the second pack and beyond, regardless of pressure or heart rate. Also, the condition of injury severity criterion score of more than 16 to enter the study will be removed.
Many critically ill patients with low blood pressure and heavy bleeding are transferred to the operating room after receiving a blood bag and receive subsequent blood bags in the operating room. These patients also benefit from this study, so patients with a systolic pressure below 80 who receive the first blood bag are also added to the conditions of entering the study
Acronym
ALMIMTP
IRCT registration information
IRCT registration number:IRCT20230707058707N1
Registration date:2023-12-06, 1402/09/15
Registration timing:prospective
Last update:2024-03-17, 1402/12/27
Update count:4
Registration date
2023-12-06, 1402/09/15
Registrant information
Name
Soheil Sahafi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 71 3656 1547
Email address
soheilsahafi515@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-12-22, 1402/10/01
Expected recruitment end date
2024-04-20, 1403/02/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluating the safety of Administration of Adenosine, Lidocaine, and Mg(ALM) cocktail among Multiple Trauma Patients receiving Massive Transfusion with dose escalation A phase I, clinical trial
Public title
Adenosine, lidocaone, and magnasium cocktail in massive transfusion patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Candidate to recieve the second pack of packed red blood cell
A candidate to receive the first bag of red blood cells who has a systolic pressure of 80 or lower
Exclusion criteria:
Severe underlying disease specially cardiac, renal, and pulmonary
Paitient with slash thoracotomy
Penetrating brain injury or exposed brain matter
Paitients with irregular base electrocardiogram
Age
From 16 years old to 60 years old
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size:
17
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Other
Other design features
This is a phase 1 clinical trial. The cocktail will be started with the minimum effective dose in a group of 4-5 patients then if the safety of the cocktail is confirmed the cocktail dose will be increased in the next three patients. The whole number of patients will be 17.
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Shiraz University of Medical Sciences
Street address
Shiraz, Islamic Republic Boulevard, Shiraz University Central Building, 5th floor
City
Shiraz
Province
Fars
Postal code
7194684471
Approval date
2023-11-25, 1402/09/04
Ethics committee reference number
IR.SUMS.REC.1402.395
Health conditions studied
1
Description of health condition studied
repairfusion injury
ICD-10 code
ICD-10 code description
Primary outcomes
1
Description
mortality
Timepoint
during hospital admission
Method of measurement
number of mortality in admited paitients
2
Description
recovery from trauma
Timepoint
At time of discharge from hospital
Method of measurement
duration of hospital admission
3
Description
amount of recieved blood
Timepoint
At the end of hospital admission
Method of measurement
amount of recieved pack cell
4
Description
amount of hemoglubin rise
Timepoint
before bolus after bolus and after drip
Method of measurement
cheking blood hemoglubin
5
Description
renal function
Timepoint
before bolus after bolus and after drip
Method of measurement
checking BUN and Cr
6
Description
improvement of clinical course
Timepoint
before bolus after bolus and after drip
Method of measurement
arterial blood gas
7
Description
severity of hemolysis
Timepoint
before bolus after bolus and after drip
Method of measurement
checking blood lactate dehydrogenase
8
Description
coagulopathy recovery
Timepoint
before bolus after bolus and after drip
Method of measurement
prothrombin time(PT), partial trombopalstin time(PTT), international normalized ratio(INR)
Secondary outcomes
empty
Intervention groups
1
Description
1st Intervention group: Adenosine lidocaine magnesium combination will be given to 4 eligible patients simultaneously with the second blood bag in two doses of bolus and infusion. If the safety of the cocktail is confirmed by the decision of the research team in the next group, the dose of the drug will be increased in next group. The cocktail dosage in first 4 patienst is as follows: the bolus dose consists of 200 cc of normal saline, 4 mg of adenosine (injected in one to two seconds with 20 cc of normal saline), 20 mg of lidocaine, 30 mg of magnesium sulfate. These compounds will be injected separately. After injecting the bolus dose, the infusion dose will be injected within 4 hours. The infusion dose will include 0.08 mg/kg/hour lidocaine, 0.09 mg/kg/hour adenosine and 0.2 mg/kg/hour magnesium. Each of these drugs will be injected in 300 cc of normal saline.
Category
Treatment - Drugs
2
Description
2end Intervention group: If the safety of the drug is confirmed in the previous stage, in this stage the dosage of the drugs will be slightly increased with the same implementation method as the previous group, which this time will be done on 5 patients. The cocktail dosage in this group is as follows: the bolus dose consists of 200 cc of normal saline, 6 mg of adenosine (injected in one to two seconds with 20 cc of normal saline), 40 mg of lidocaine, 30 mg of magnesium sulfate(Magnesium sulfate calculated by the clinical pharmacologist is much lower than the minimum effective dose in the clinic, so it does not need to gradually increase the dose). These compounds will be injected separately. After injecting the bolus dose, the infusion dose will be injected within 4 hours. The infusion dose will include 0.1 mg/kg/hour lidocaine, 0.12 mg/kg/hour adenosine and 0.2 mg/kg/hour magnesium. Each of these drugs will be injected in 300 cc of normal saline.
Category
Treatment - Drugs
3
Description
3rd Intervention group: If the safety of the drug is confirmed in the previous stage, in this stage the dosage of the drugs will be slightly increased with the same implementation method as the previous group, which this time will be done on 4 patients. The cocktail dosage in this group is as follows: the bolus dose consists of 200 cc of normal saline, 9 mg of adenosine (injected in one to two seconds with 20 cc of normal saline), 60 mg of lidocaine, 30 mg of magnesium sulfate(Magnesium sulfate calculated by the clinical pharmacologist is much lower than the minimum effective dose in the clinic, so it does not need to gradually increase the dose). These compounds will be injected separately. After injecting the bolus dose, the infusion dose will be injected within 4 hours. The infusion dose will include 0.13 mg/kg/hour lidocaine, 0.14 mg/kg/hour adenosine and 0.2 mg/kg/hour magnesium. Each of these drugs will be injected in 300 cc of normal saline.
Category
Treatment - Drugs
4
Description
4th Intervention group: If the safety of the drug is confirmed in the previous stage, in this stage the dosage of the drugs will be slightly increased with the same implementation method as the previous group, which this time will be done on 4 patients. The cocktail dosage in this group is as follows: the bolus dose consists of 200 cc of normal saline, 12 mg of adenosine (injected in one to two seconds with 20 cc of normal saline), 87 mg of lidocaine, 30 mg of magnesium sulfate(Magnesium sulfate calculated by the clinical pharmacologist is much lower than the minimum effective dose in the clinic, so it does not need to gradually increase the dose). These compounds will be injected separately. After injecting the bolus dose, the infusion dose will be injected within 4 hours. The infusion dose will include 0.16 mg/kg/hour lidocaine, 0.16 mg/kg/hour adenosine and 0.2 mg/kg/hour magnesium. Each of these drugs will be injected in 300 cc of normal saline.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Shahid Rajaee Trauma Hospital
Full name of responsible person
Behzad Moazeni
Street address
Chyamran Blvd, Shahid Rajaee Hospital
City
Shiraz
Province
Fars
Postal code
7194815711
Phone
+98 71 3636 4001
Email
rajaeehopital@sums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Seyed Vahid Hosseini
Street address
Zand Blvd, Shiraz Univercity Of Medical science
City
Shiraz
Province
Fars
Postal code
7134814336
Phone
+98 71 3230 5410
Email
info@sums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Shiraz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Seyed Soheil Sahafi
Position
medical intern
Latest degree
A Level or less
Other areas of specialty/work
General Practitioner
Street address
No. 286, 8th Ave., Molana Blvd., Sadra town
City
Shiraz
Province
Fars
Postal code
7199731554
Phone
+98 71 3656 1547
Email
soheilsahafi515@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Seyed Soheil Sahafi
Position
Medical Intern
Latest degree
A Level or less
Other areas of specialty/work
General Practitioner
Street address
No 286, 8th Ave, Molana Blvd., Sadra town
City
Shiraz
Province
Fars
Postal code
7199731554
Phone
00986561547
Email
soheilsahafi515@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Seyed Soheil Sahafi
Position
Medical Intern
Latest degree
A Level or less
Other areas of specialty/work
General Practitioner
Street address
No 286, 8th Ave, Molana Blvd., Sadra town
City
Shiraz
Province
Fars
Postal code
7199731554
Phone
+98 71 3656 1547
Email
soheilsahafi515@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be 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
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be 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
Undecided - It is not yet known if there will be a plan to make this available