History
# Registration date Revision Id
2 2022-01-16, 1400/10/26 213487
1 2016-01-22, 1394/11/02 9118
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  • Protocol summary

    Cyclosporine as an immunosuppressive drug is widely used in patient undergoing transplant surgeries. Glioblastoma multiforme is one of the aggressive tumors that still has no pivotal treatment. In animal models the effect of cyclosporine on preventing tumor growth and invasion is observed. These studies are in the initial phase of the clinical trial and efficacy of the drug in humans has not been established yet. This study is designed to evaluate the efficacy of cyclosporine on preventing tumor growth and invasion of GBM. The study is a single blind randomized clinical trial. Survival of patients after one year of treatment in this study will be presented. For this purpose, patients whom brain MRI and intraoperative frozen section represent the GBM diagnosis would be treated with cyclosporine. The drug delivery starts immediately after the surgery with the dose of Neuroprotective effects in trauma cases which is documented in literature. Infusion of 2.5 mg/kg over first 2 hours and will be continued with the dose of 5mg/kg /day for 72 hours. In this study, 40 patients will be recruited and will be visited every month and evaluated with Karnofsky score. Any decline in the indicators of this scale is recorded. Based on tumor location and amount of tumor resection patients are classified into SUBTOTAL, NEAR TOTAL & GTR. The beneficial effect of cyclosporine on 1 year survival of patients will be evaluated with Karnofsky score.
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    داروی سیکلوسپورین از دسته داروهای سرکوب کننده ایمنی میباشد که به طور وسیع در بیماران تحت جراحی های پیوند استفاده میشود. گلیوبلاستوم مولتی فرم از دسته تومورهای تهاجمی میباشد که هنوز درمان مهمی برای آن ارایه نشده است. در مدلهای حیوانی تاثیر داروی سیکلوسپورین بر جلوگیری از رشد و تهاجم تومور مشاهده شده است. این مطالعات فازهای ابتدایی کارآزمایی بالینی بوده است و هنوز مطالعه اثربخشی این دارو در انسان انجام نشده است. این مطالعه به منظور بررسی اثربخشی داروی سیکلوسپورین بر جلوگیری از رشد وتهاجم تومور گلیوبلاستوم طراحی شد. بقا یک ساله بیماران بعد از درمان در این مطالعه ارایه خواهد شده است و به صورت کارآزمایی یکسو کور و تصادفی است. برای این منظور بیمارانی که بر اساس تصویر برداری ام ار ای و نمونه بافتی منجمد حین عمل جراحی تشخیص تومور گلیوبلاستوم برایش گذاشته می شود تحت درمان با داروی سیکلوسپورین قرار می گیرند. برای این بیماران دارو با دوز موثر نوروپروتکتیو تروما که در منابع موجود است بلافاصله پس از جراحی شروع می گردد.2.5mg/kg در طی 2 ساعت برای بیمار انفوزیون می شود و سپس با دوز 5mg/kg در روز برای 72 ساعت جهت بیمار ادامه می یابد. 40 بیمار در مطالعه وارد می شوند و بیماران در فواصل یک ماهه ویزیت می شوند و از نظر معیار کارنوفسکی به شکل بالینی مورد ارزیابی قرار می گیرند. هر گونه کاهش در این شاخص مورد ارزیابی قرارمیگیرد. بیماران بر اساس محل تومور و میزان تخلیه تومور به شکل GTR , NEAR TOTAL ,SUBTOTAL طبقه بندی می شوند و پس از بررسی اثرات تجویز داروی سیکلوسپورین بر بقای 1 ساله بیماران بر اساس معیار کارنوفسکی مورد ارزیابی قرار می گیرند.
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    Evaluation of the efficacy and side effects of cyclosporine in the treatment of patients with glioblastoma multiforme
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    بررسی اثربخشی و عوارض سیکلوسپورین در درمان بیماران مبتلا به گلیوبلاستوما مولتی فرم
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    Two arm parallel groups, randomised trial with blinded postoperative care and outcome assessment, phase 2-3 on 99 patients. Computer sequencing was used for randomization.
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    کارآزمایی بالینی دارای گروه کنترل، با گروه های موازی ، سه سویه کور ، تصادفی شده، فاز 2-3 بر روی 99بیمار. برای تصادفی سازی از توالی کامپیوتری استفاده شد.
    empty
    Patients referred to Shariati Hospital in Tehran, who were definitively diagnosed with glioblastoma based on frozen section surgery, were randomly alocated to the study. Patients then received envelopes labeled A and B containing the cyclosporine or placebo. In this study, patients, researchers and analyzers were not aware of the individuals assigned to the study groups.
    empty
    بیماران مراجعه کننده به بیمارستان شریعتی تهران که برای ایشان تشخیص قطعی گلیوبلاستوما بر اساس نتیجه نمونه حین جراحی داده شد، به صورت تصادفی وارد مطالعه شدند. سپس بیماران پاکت هایی با برچسب A و B که حاوی داروی سیکلوسپورین و یا دارونما بود دریافت کردند. در این مطالعه، بیماران، محقق و آنالیزور از اختصاص افراد به گروههای مورد مطالعه اطلاعی نداشتند.
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    Inclusion criteria: 1. Age over 18 years 2. Definitive diagnosis of glioblastoma tumor Exclusion criteria: 1. History of previous brain tumor surgery 2. Receive previous chemotherapy 3. Pregnancy 4. Breastfeeding 5. Immune defect 6. Active infection 7. Hepatitis
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    شرایط ورود: 1. سن بیشتر از 18 سال 2. تشخیص قطعی تومور گلیوبلاستوما شرایط عدم ورود: 1. سابقه جراحی قبلی تومور مغزی 2. دریافت شیمی درمانی قبلی 3. حاملگی 4. شیردهی 5. نقص ایمنی 6. عفونت فعال 7. هپاتیت
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    Intervention group: Injectable cyclosporine (2.5 mg / kg for 2 hours for the patient and then infused at a dose of 5 mg / kg per day for 72 hours) Control group: receiving placebo
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    گروه مداخله: سیکلوسپورین تزریقی (2.5mg/kg در طی 2 ساعت برای بیمار انفوزیون می شود و سپس با دوز 5mg/kg در روز برای 72 ساعت) گروه کنترل: دریافت دارونما
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    Overall survival Progression-free survival One year survival Performanc status (Karnovsky score)
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    بقای کلی بقای بدون پیشرفت بیماری بقای یکساله وضعیت عملکردی (نمره کارنوفسکی)
  • General information

    90
    empty
    Year
    empty
    No
    Yes
    Single blinded
    Triple blinded
    1
    1
    1
    1
    1
    Not used
    Used
    2
    2-3
    empty
    99
    empty
    2014-07-23, 1393/05/01
    empty
    2017-04-21, 1396/02/01
    empty
    2020-03-20, 1399/01/01
    empty
    Regarding the completion of the study, some conditions related to the design of the study were updated. 1. The study was conducted as triple blind. 2. In addition to standard treatment, the control group also received a placebo.
    empty
    با توجه به اتمام مطالعه برخی از شرایط مربوط به طراحی مطالعه به روزرسانی شد. 1. مطالعه به صورت سه سوکور انجام شد. 2. گروه کنترل علاوه بر درمان استاندارد، دارونما نیز دریافت کرد/
    Age over 18 years
    No history of surgery and/or previous chemoteraphy
    Confirmed diagnosis of gliobalstoma
    سن بیشتر از 18 سال
    عدم سابقه جراحی قبلی و یا دریافت شیمی درمانی
    تشخیص قطعی گلیوبلاستوما
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    A computer-generated sequence with a block size of 4 patients was used for randomization. The patients were assigned consecutive numbers based on their order of enrolment in the study. Thus, unblinded pharmacists who were otherwise uninvolved in study conduct obtained randomized treatment assignments and managed study treatment
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    یک توالی کامپیوتری با اندازه بلوک 4 بیمار جهت تصادفی سازی استفاده شد. به بیماران بر اساس ترتیب ثبت نام در مطالعه شماره های متوالی اختصاص داده شد. بنابراین، یک فرد داروساز که در مطالعه شرکت نداشت، تصادفی سازی و اختصاص افراد به گروههای درمان و دارونما را انجام داد.
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    Patients were allocated to group A and B and received envelopes labeled A and B that contained Cyclosporine or placebo after surgery. Hence, neither the patients nor all investigators were aware of the drug contents and group allocation.
    empty
    بیماران به گروه A و B تقسیم شدند و پس از جراحی پاکت هایی با برچسب A و B دریافت کردند که حاوی سیکلوسپورین یا دارونما بود. از این رو، نه بیماران و نه همه محققان از محتویات دارو و تخصیص گروه ها آگاه نبودند.
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  • Recruitment centers

    #1
    Name of recruitment center - English: Shariati Hospital
    Name of recruitment center - Persian: بیمارستان شریعتی
    Full name of responsible person - English: Dr Khoshnevisan
    Full name of responsible person - Persian: دکتر خوشنویسان
    Street address - English:
    Street address - Persian:
    City - English: Tehran
    City - Persian: تهران
    Province:
    Country: Iran (Islamic Republic of)
    Postal code:
    Phone:
    Fax:
    Email:
    Web page address:
    Name of recruitment center - English: Shariati Hospital
    Name of recruitment center - Persian: بیمارستان شریعتی
    Full name of responsible person - English: Dr Khoshnevisan
    Full name of responsible person - Persian: دکتر خوشنویسان
    Street address - English: جلال آل احمد
    Street address - Persian: Jala-al-ahmad Ave
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Country: Iran (Islamic Republic of)
    Postal code: 1411713135
    Phone: +98 21 8490 1000
    Fax:
    Email: akhoshnevisan@tums.ac.ir
    Web page address:
  • Sponsors / Funding sources

    #1
    contact.organization_id:
    Name of organization / entity - English: Tehran University of Medical Sciences
    Name of organization / entity - Persian: دانشگاه علوم پزشکی تهران
    Full name of responsible person - English: Dr khoshnevisan
    Full name of responsible person - Persian: دکتر خوشنویسان
    Street address - English: Shariati Hospital
    Street address - Persian: بیمارستان شریعتی
    City - English: Tehran
    City - Persian: تهران
    Province:
    Country: Iran (Islamic Republic of)
    Postal code:
    Phone:
    Fax:
    Email:
    Web page address:
    contact.organization_id:
    Name of organization / entity - English: Tehran University of Medical Sciences
    Name of organization / entity - Persian: دانشگاه علوم پزشکی تهران
    Full name of responsible person - English: Dr khoshnevisan
    Full name of responsible person - Persian: دکتر خوشنویسان
    Street address - English: Shariati Hospital
    Street address - Persian: بیمارستان شریعتی
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Country: Iran (Islamic Republic of)
    Postal code: 1411713135
    Phone: +98 21 8490 1000
    Fax:
    Email: akhoshnevisan@tums.ac.ir
    Web page address:
    empty
    Public
    empty
    Domestic
    empty
    Academic
  • Person responsible for general inquiries

    contact.organization_id:
    Name of organization / entity - English: Tehran University of Medical Science
    Name of organization / entity - Persian: دانشگاه علوم پزشکی تهران
    Full name of responsible person - English: Dr Farzaneh
    Full name of responsible person - Persian: دکتر فرزانه
    Position - English: MD
    Position - Persian: پزشک
    Latest degree:
    Area of specialty/work: 0
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Shariati Hospital
    Street address - Persian: بیمارستان شریعتی
    City - English: Tehran
    City - Persian: تهران
    Province:
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code:
    Phone: +98 21 8490 2272
    Mobile: 00
    Fax:
    Email: ff1353@yahoo.com
    Web page address:
    contact.organization_id:
    Name of organization / entity - English: Tehran University of Medical Science
    Name of organization / entity - Persian: دانشگاه علوم پزشکی تهران
    Full name of responsible person - English: Dr Farzaneh
    Full name of responsible person - Persian: دکتر فرزانه
    Position - English: MD
    Position - Persian: پزشک
    Latest degree: specialist
    Area of specialty/work: 37
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Shariati Hospital
    Street address - Persian: بیمارستان شریعتی
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 1411713135
    Phone: +98 21 8490 1000
    Mobile: +98 912 154 2588
    Fax:
    Email: ff1353@yahoo.com
    Web page address:
  • Person responsible for scientific inquiries

    contact.organization_id:
    Name of organization / entity - English: Tehran University of Medical Sciences
    Name of organization / entity - Persian: دانشگاه علوم پزشکی تهران
    Full name of responsible person - English: Dr Khoshnevisan
    Full name of responsible person - Persian: دکتر خوشنویسان
    Position - English: MD
    Position - Persian: پزشک
    Latest degree:
    Area of specialty/work: 0
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Shariati Hospital
    Street address - Persian: بیمارستان شریعتی
    City - English: Tehran
    City - Persian: تهران
    Province:
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code:
    Phone: +98 21 8490 2272
    Mobile: 00
    Fax:
    Email: akhoshnevisan@yahoo.com
    Web page address:
    contact.organization_id:
    Name of organization / entity - English: Tehran University of Medical Sciences
    Name of organization / entity - Persian: دانشگاه علوم پزشکی تهران
    Full name of responsible person - English: Dr Khoshnevisan
    Full name of responsible person - Persian: دکتر خوشنویسان
    Position - English: MD
    Position - Persian: پزشک
    Latest degree: specialist
    Area of specialty/work: 37
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Shariati Hospital
    Street address - Persian: بیمارستان شریعتی
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 1411713135
    Phone: +98 21 8490 1000
    Mobile: +98 912 100 7205
    Fax:
    Email: akhoshnevisan@yahoo.com
    Web page address:
  • Person responsible for updating data

    contact.organization_id:
    Name of organization / entity - English: Tehran University of Medical Sciences
    Name of organization / entity - Persian: دانشگاه علوم پزشکی تهران
    Full name of responsible person - English: Dr Farzaneh
    Full name of responsible person - Persian: دکتر فرزانه
    Position - English: MD
    Position - Persian: پزشک
    Latest degree:
    Area of specialty/work: 0
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Shariati Hospital
    Street address - Persian: بیمارستان شریعتی
    City - English: Tehran
    City - Persian: تهران
    Province:
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code:
    Phone: +98 21 8490 2272
    Mobile: 00
    Fax:
    Email:
    Web page address:
    contact.organization_id:
    Name of organization / entity - English: Tehran University of Medical Sciences
    Name of organization / entity - Persian: دانشگاه علوم پزشکی تهران
    Full name of responsible person - English: Dr Farzaneh
    Full name of responsible person - Persian: دکتر فرزانه
    Position - English: MD
    Position - Persian: پزشک
    Latest degree: specialist
    Area of specialty/work: 37
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Shariati Hospital
    Street address - Persian: بیمارستان شریعتی
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 1411713135
    Phone: +98 21 8490 1000
    Mobile: +98 912 154 2588
    Fax:
    Email: ff1353@yahoo.com
    Web page address:
  • Sharing plan

    yes
    yes
    yes
    yes
    yes
    yes
    yes
    empty
    Publish as scintifice article
    empty
    چاپ تمامی موارد در قالب مقاله علمی
    empty
    from 2021
    empty
    از سال 1400 به بعد
    empty
    Researchers
    empty
    محققان
    empty
    To design future studies
    empty
    جهت کمک به طراحی مطالعات بعدی
    empty
    Dr. Alireza Khoshnevisan
    empty
    دکتر علیرضا خوشنویسان
    empty
    Formal request to principal researcher of study
    empty
    درخواست کتبی به محقق اصلی مطالعه

Protocol summary

Study aim
Evaluation of the efficacy and side effects of cyclosporine in the treatment of patients with glioblastoma multiforme
Design
Two arm parallel groups, randomised trial with blinded postoperative care and outcome assessment, phase 2-3 on 99 patients. Computer sequencing was used for randomization.
Settings and conduct
Patients referred to Shariati Hospital in Tehran, who were definitively diagnosed with glioblastoma based on frozen section surgery, were randomly alocated to the study. Patients then received envelopes labeled A and B containing the cyclosporine or placebo. In this study, patients, researchers and analyzers were not aware of the individuals assigned to the study groups.
Participants/Inclusion and exclusion criteria
Inclusion criteria: 1. Age over 18 years 2. Definitive diagnosis of glioblastoma tumor Exclusion criteria: 1. History of previous brain tumor surgery 2. Receive previous chemotherapy 3. Pregnancy 4. Breastfeeding 5. Immune defect 6. Active infection 7. Hepatitis
Intervention groups
Intervention group: Injectable cyclosporine (2.5 mg / kg for 2 hours for the patient and then infused at a dose of 5 mg / kg per day for 72 hours) Control group: receiving placebo
Main outcome variables
Overall survival Progression-free survival One year survival Performanc status (Karnovsky score)

General information

Reason for update
Regarding the completion of the study, some conditions related to the design of the study were updated. 1. The study was conducted as triple blind. 2. In addition to standard treatment, the control group also received a placebo.
Acronym
IRCT registration information
IRCT registration number: IRCT201512028612N3
Registration date: 2016-01-22, 1394/11/02
Registration timing: registered_while_recruiting

Last update: 2022-01-18, 1400/10/28
Update count: 1
Registration date
2016-01-22, 1394/11/02
Registrant information
Name
Amir Sarayani
Name of organization / entity
Research Center for Rational Use of Drugs
Country
Iran (Islamic Republic of)
Phone
+98 21 8881 4157
Email address
a-sarayanib@razi.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Tehran University of Medical Science, Shariati Hospital
Expected recruitment start date
2014-07-23, 1393/05/01
Expected recruitment end date
2016-04-20, 1395/02/01
Actual recruitment start date
2014-07-23, 1393/05/01
Actual recruitment end date
2017-04-21, 1396/02/01
Trial completion date
2020-03-20, 1399/01/01
Scientific title
A Clinical trial to assess the effects of short-term administration of cyclosporine on survival of patients with glioblastoma multiforme tumor surgery
Public title
Effect of an immuno-suppresive medication (cyclosporine) on brain tumor patients survival
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age over 18 years No history of surgery and/or previous chemoteraphy Confirmed diagnosis of gliobalstoma
Exclusion criteria:
Age
From 18 years old
Gender
Both
Phase
2-3
Groups that have been masked
  • Participant
  • Care provider
  • Investigator
  • Outcome assessor
  • Data analyser
Sample size
Target sample size: 40
Actual sample size reached: 99
Randomization (investigator's opinion)
Randomized
Randomization description
A computer-generated sequence with a block size of 4 patients was used for randomization. The patients were assigned consecutive numbers based on their order of enrolment in the study. Thus, unblinded pharmacists who were otherwise uninvolved in study conduct obtained randomized treatment assignments and managed study treatment
Blinding (investigator's opinion)
Triple blinded
Blinding description
Patients were allocated to group A and B and received envelopes labeled A and B that contained Cyclosporine or placebo after surgery. Hence, neither the patients nor all investigators were aware of the drug contents and group allocation.
Placebo
Used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Tehran University of Medical Sciences, Ethics Committee
Street address
Ghods junction, Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1411713135
Approval date
2015-06-17, 1394/03/27
Ethics committee reference number
IR.TUMS.REC.1394.76

Health conditions studied

1

Description of health condition studied
glioblastoma multiform
ICD-10 code
C71.9
ICD-10 code description
Malignant neoplasm of brain/unspecified

Primary outcomes

1

Description
Performance Status (Survival)
Timepoint
measured every 2 months after recruitment up to one year
Method of measurement
Karnofsky Performance Status Scale

Secondary outcomes

empty

Intervention groups

1

Description
Infusion of 2.5 mg/kg cyclosporine over first 2 hours post operation and will be continued with the dose of 5mg/kg /day for 72 hours
Category
Treatment - Drugs

2

Description
control group: routine care of post op GBM patients
Category
Other

Recruitment centers

1

Recruitment center
Name of recruitment center
Shariati Hospital
Full name of responsible person
Dr Khoshnevisan
Street address
جلال آل احمد
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Email
akhoshnevisan@tums.ac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr khoshnevisan
Street address
Shariati Hospital
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Email
akhoshnevisan@tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran 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
Tehran University of Medical Science
Full name of responsible person
Dr Farzaneh
Position
MD
Latest degree
Specialist
Other areas of specialty/work
Neurosurgery
Street address
Shariati Hospital
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Fax
Email
ff1353@yahoo.com
Web page address

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr Khoshnevisan
Position
MD
Latest degree
Specialist
Other areas of specialty/work
Neurosurgery
Street address
Shariati Hospital
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Fax
Email
akhoshnevisan@yahoo.com
Web page address

Person responsible for updating data

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr Farzaneh
Position
MD
Latest degree
Specialist
Other areas of specialty/work
Neurosurgery
Street address
Shariati Hospital
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Fax
Email
ff1353@yahoo.com
Web page address

Sharing plan

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
Yes - There is 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
Yes - There is a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
Publish as scintifice article
When the data will become available and for how long
from 2021
To whom data/document is available
Researchers
Under which criteria data/document could be used
To design future studies
From where data/document is obtainable
Dr. Alireza Khoshnevisan
What processes are involved for a request to access data/document
Formal request to principal researcher of study
Comments
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