Clinical Trial Protocol Iranian Registry of Clinical Trials

29 Sep 2021

Randomzied trial of additional treatments for COVID-19 in hospitalized patients who are all receiving the local standard of care- Iranian SOLIDARITY multicentre trial

Protocol summary Main outcome variables Main Outcome: All-cause mortality Major Secondary Study aim Outcomes: -Duration of hospitalization -Time to Main Aim: To evaluate the safety and efficacy of ventilation (ICU Care) medications in treating COVID-19 Specific Aims: -To evaluate the safety and efficacy of Remdesivir in treating General information COVID-19 -To evaluate the safety and efficacy of Chloroquine/Hydroxychloroquine in treating COVID-19 - Reason for update To evaluate the safety and efficacy of Lopinovir/Retinovir Acronym in treating COVID-19 -To evaluate the safety and efficacy IRCT registration information of Lopinovir/Retinovir along with Interferon in treating IRCT registration number: IRCT20200405046953N1 COVID-19 -To compare the efficacy of medications in Registration date: 2020-04-06, 1399/01/18 treating COVID-19 Registration timing: prospective Design Five-Arm, Multi-center, randomized controlled trial Last update: 2020-04-06, 1399/01/18 Settings and conduct Update count: 0 This trial will be performed in 30 hospitals throughout Registration date Iran. Clinicians will randomize patients using the study 2020-04-06, 1399/01/18 website and provide the appropriate treatment per protocol. Registrant information Participants/Inclusion and exclusion criteria Name Inclusion Criteria: -Adults (age ≥18) -Hospitalised with Hossein Poustchi definite COVID-19 diagnosis, not already receiving any of Name of organization / entity the study medications -No known allergy or Country contraindications to any of the study medications - Iran (Islamic Republic of) Patients admitted to collaborating hospitals, without Phone anticipated transfer within 72 hours Exclusion Criteria: - +98 21 8241 5204 Anyone having a significant contraindication to any one Email address of the study drugs -Serious chronic liver or heart disease [email protected] -Pregnancy Intervention groups Recruitment status • Local standard of care alone OR local standard of care Recruitment complete plus one of: • Remdesivir (daily infusion for 10 days) • Funding source Chloroquine or Hydroxychloroquine (two oral loading doses, then orally twice daily for 10 days) [NB Some Expected recruitment start date collaborating hospitals will study chloroquine, others 2020-04-08, 1399/01/20 hydroxychloroquine] • Lopinavir with Ritonavir (orally Expected recruitment end date twice daily for 14 days) • Lopinavir with Ritonavir (ditto) 2020-06-09, 1399/03/20 plus Interferon (daily injection for 6 days). Actual recruitment start date

1 empty Other design features Actual recruitment end date empty Secondary Ids Trial completion date empty empty

Scientific title Ethics committees Randomzied trial of additional treatments for COVID-19 in hospitalized patients who are all receiving the local standard of care- Iranian SOLIDARITY multicentre trial 1

Public title Ethics committee Comparison of therapies for COVID-19 Name of ethics committee Purpose National Institute for Medical Research Development Treatment (NIMAD) Inclusion/Exclusion criteria Street address Inclusion criteria: No. 21, Be'sat Alley, East Fatemi St. , Iran Adults (age ≥18) Hospitalised with definite COVID-19 City diagnosis, not already receiving any of the study Tehran medications No known allergy or contraindications to any Province of the study medications Patients admitted to Tehran collaborating hospitals, without anticipated transfer Postal code within 72 hours 1419693111 Exclusion criteria: Approval date Anyone having a significant contraindication to any one 2020-04-02, 1399/01/14 of the study drugs Serious chronic liver or heat disease Ethics committee reference number Pregnancy IR.NREC.1399.001 Age From 18 years old Health conditions studied Gender Both 1 Phase 3 Description of health condition studied Groups that have been masked COVID-19 No information ICD-10 code Sample size U07.1 Target sample size: 3000 ICD-10 code description Randomization (investigator's opinion) COVID-19 Randomized Randomization description Primary outcomes Given that this study is part of the SOLIDARITY Trial by the World Health Organization, the randomization method is only known by the Principal Investigators. 1 Patients will be randomized through the study website Description equally between all the locally available treatment Primary Outcome: All-cause mortality regimens (5 possibilities if all study drugs are locally Timepoint available, fewer if not) • Local standard of care alone, OR Any time death or discharge of patients occurs local standard of care plus one of • Remdesivir (daily Method of measurement infusion for 10 days) • Chloroquine or Death certificate signed by hospital clinicians or Hydroxychloroquine (two oral loading doses, then orally discharge documents twice daily for 10 days) [NB Some collaborating hospitals will study chloroquine, others hydroxychloroquine] • Lopinavir with Ritonavir (orally twice daily for 14 days) • Secondary outcomes Lopinavir with Ritonavir (ditto) plus Interferon (daily injection for 6 days). 1 Blinding (investigator's opinion) Not blinded Description Blinding description Duration of Hospital Stay Placebo Timepoint Not used Any time during the study Assignment Method of measurement Parallel Based on Medical Charts

2 2 City Tehran Description Province Time to ventilation (ICU Care) Tehran Timepoint Postal code Any time during the study 1111111111 Method of measurement Email Based on Medical Chart [email protected] Intervention groups 2

1 Recruitment center Name of recruitment center Description Imam Khomeini Hospital Complex Intervention group: local standard of care plus Full name of responsible person Remdesivir (daily infusion for 10 days) Mohammad Reza Salehi Category Street address Treatment - Drugs Keshavarz Blvd. Dr. Gharib St. City 2 Tehran Province Description Tehran Intervention group: local standard of care plus Postal code Chloroquine or Hydroxychloroquine (two oral loading 1419733141 doses, then orally twice daily for 10 days) Email Category [email protected] Treatment - Drugs

3 3 Description Recruitment center Intervention group: local standard of care plus Lopinavir Name of recruitment center with Ritonavir (orally twice daily for 14 days) Loghman Hakim Hospital Category Full name of responsible person Treatment - Drugs Ilad Alavi Darazam Street address Karegare Jonoobi Ave, Lashgar , Makhsoos St. 4 City Description Tehran Intervention group: local standard of care plus Lopinavir Province with Ritonavir (ditto) plus Interferon (daily injection for 6 Tehran days). Postal code Category 1333635445 Treatment - Drugs Email [email protected] 5 Description 4 Control group: local standard of care Recruitment center Category Name of recruitment center Treatment - Drugs FIroozgar Hospital Full name of responsible person Recruitment centers Mitra Ranjbar Street address Valiasr Sq. Karimkhan St. Beh Afarin St. 1 City Recruitment center Tehran Name of recruitment center Province Baharloo Hospital Tehran Full name of responsible person Postal code Hadiseh Hosami 1593747811 Street address Email Behdari St. [email protected]

3 5 City Mashhad Recruitment center Province Name of recruitment center Razavi Khorasan Masih Danesvari Hospital Postal code Full name of responsible person 9351899983 Payam Tabarsi Email Street address [email protected] Shahid Bahonar St. Darabad St. City Tehran 9 Province Recruitment center Tehran Name of recruitment center Postal code Ali Asghar Hospital 1956944413 Full name of responsible person Email Mohsen Moghadami [email protected] Street address Meshkin Fam St. 6 City Recruitment center Shiraz Name of recruitment center Province Imam Ali Hospital Fars Full name of responsible person Postal code Alireza Soleimani 7143918796 Street address Email Intersection [email protected] City Karaj 10 Province Recruitment center Alborz Name of recruitment center Postal code Chamran Hospital 3154686695 Full name of responsible person Email Mohsen Moghadami [email protected] Street address Shahid Chamran Blvd. 7 City Recruitment center Shiraz Name of recruitment center Province Imam Reza Hospital Fars Full name of responsible person Postal code Mahnaz Amini 7194815644 Street address Email Imam Reza Square [email protected] City Mashhad 11 Province Razavi Khorasan Recruitment center Postal code Name of recruitment center 9137913316 Shahid Beheshti Email Full name of responsible person [email protected] Ahmad Hormati Street address Shahid Beheshti Sq. Azadegan Blvd. 8 City Recruitment center Qom Name of recruitment center Province Shariati Hospital Ghoum Full name of responsible person Postal code Saeid Hafizi Lotfabadi 1111111111 Street address Email Vakil Abad Ave. Imam Reza Alley [email protected]

4 12 City Isfahan Recruitment center Province Name of recruitment center Isfehan Kamkar Hospital Postal code Full name of responsible person 8174675731 Mohammad Reza Ghadir Email Street address [email protected] Dey 19th St. City Qom 16 Province Recruitment center Ghoum Name of recruitment center Postal code Khorshid Hospital 1111111111 Full name of responsible person Email Kiana Shirani [email protected] Street address Ostandari St. 13 City Recruitment center Isfahan Name of recruitment center Province Shahid Sadoughi Hospital Isfehan Full name of responsible person Postal code Alireza Musavi 1111111111 Street address Email Shahid Ghandi Blvd. Ebn Sina St. [email protected] City Yazd 17 Province Recruitment center Yazd Name of recruitment center Postal code Amin Hospital 8915887857 Full name of responsible person Email Atousa Hakami Fard [email protected] Street address Ebne Sina St. 14 City Recruitment center Isfahan Name of recruitment center Province Imam Reza Hospital Isfehan Full name of responsible person Postal code Khalil Ansarin 1111111111 Street address Email Golgasht St. [email protected] City Tabriz 18 Province East Azarbaijan Recruitment center Postal code Name of recruitment center 5166614756 Esabne Maryam Hospital Email Full name of responsible person [email protected] Mehrdad Salahi Street address Shams Abadi St. 15 City Recruitment center Isfahan Name of recruitment center Province Alzahra Hospital Isfehan Full name of responsible person Postal code Farzin Khorvash 1111111111 Street address Email Sofeh Blvd. [email protected]

5 19 City Gorgan Recruitment center Province Name of recruitment center Golestan Razi Hospital Postal code Full name of responsible person 1111111111 Fariborz Mansour Ghanaie Email Street address [email protected] Sardare Jangal St. City Rasht 23 Province Recruitment center Guilan Name of recruitment center Postal code Baghiyatallah Hospital 41448 Full name of responsible person Email Mostafa Ghanei [email protected] Street address Sq. Molasadra St. 20 City Recruitment center Tehran Name of recruitment center Province Razi Hospital Tehran Full name of responsible person Postal code Farhang Baba Mahmoodi 1435915371 Street address Email Yusef Reza St. [email protected] City Ghaem Shahr 24 Province Recruitment center Mazandaran Name of recruitment center Postal code Ayatollah Khansari Hospital 1111111111 Full name of responsible person Email Hossein Sarmadian [email protected] Street address Daneshgah St. 21 City Recruitment center Arak Name of recruitment center Province Imam Khomeini Hospital Markazi Full name of responsible person Postal code Roya Ghasemian 1111111111 Street address Email Imam St. Amir Mazandarani St. [email protected] City Sari 25 Province Mazandaran Recruitment center Postal code Name of recruitment center 4816633131 Valiasr Hospital Email Full name of responsible person [email protected] Behnam Mahmoodieh Street address Hazrate Valiasr Sq. 22 City Recruitment center Arak Name of recruitment center Province Shayyad Shirazi Hospital Markazi Full name of responsible person Postal code Behnaz Khodabakhshi 3814957558 Street address Email Shahid Sayad Shirazi Blvd. [email protected]

6 26 City Saveh Recruitment center Province Name of recruitment center Markazi Ayatollah Rohani Hospital Postal code Full name of responsible person 1111111111 Mostafa Javanian Email Street address [email protected] Ganj Afrooz St. City Babol 30 Province Recruitment center Mazandaran Name of recruitment center Postal code Boo Ali Sina Hospital 4717647745 Full name of responsible person Email HamidReza Najjari [email protected] Street address BooAli St. 27 City Qazvin Recruitment center Province Name of recruitment center Qazvin Yahyanejad Hospital Postal code Full name of responsible person 1111111111 Mostafa Javanian Email Street address [email protected] Modaras St. Mostafa Khomeini St. City Babol Sponsors / Funding sources Province Mazandaran 1 Postal code 1111111111 Sponsor Email Name of organization / entity [email protected] Iranian Ministry of Health and Medical Education, Deputy of Research and Technology Full name of responsible person 28 Reza Malekzadeh Recruitment center Street address Name of recruitment center Shahrake Gharb, Falamak St. Modarres Hospital City Full name of responsible person Tehran Hassan Mozaffar Province Street address Tehran Motahari St. Modares Blvd. Postal code City 1111111111 Saveh Phone Province +98 21 8241 5000 Markazi Email Postal code [email protected] 1111111111 Grant name Email Grant code / Reference number Hassan.mozaff[email protected] Is the source of funding the same sponsor organization/entity? Yes 29 Title of funding source Recruitment center Iranian Ministry of Health and Medical Education, Deputy Name of recruitment center of Research and Technology Shahid Chamran Hospital Proportion provided by this source Full name of responsible person 50 Mehdi Mesri Public or private sector Street address Public Tehran Old Route, Golha Route Domestic or foreign origin

7 Domestic Person responsible for updating data Category of foreign source of funding empty Contact Country of origin Name of organization / entity Type of organization providing the funding Tehran University of Medical Sciences Other Full name of responsible person Hossein Poustchi Position Person responsible for general inquiries Associate Professor Latest degree Contact Ph.D. Name of organization / entity Other areas of specialty/work Tehran University of Medical Sciences Epidemiology Full name of responsible person Street address Hossein Poustchi Karegare Shomali St. Shariati Hospital Position City Associate Professor Tehran Latest degree Province Ph.D. Tehran Other areas of specialty/work Postal code Epidemiology 1411713135 Street address Phone Karegare Shomali St. Shariati Hospital +98 21 8241 5204 City Email Tehran [email protected] Province Tehran Sharing plan Postal code 1411713135 Deidentified Individual Participant Data Set (IPD) Phone No - There is not a plan to make this available +98 21 8241 5204 Justification/reason for indecision/not sharing IPD Email Data collected in this study belongs to the World Health [email protected] Organization SOLIDARITY Trial. Study Protocol Yes - There is a plan to make this available Person responsible for scientific Statistical Analysis Plan inquiries No - There is not a plan to make this available Informed Consent Form Contact Yes - There is a plan to make this available Name of organization / entity Clinical Study Report Tehran University of Medical Sciences Not applicable Full name of responsible person Analytic Code Minoo Mohraz No - There is not a plan to make this available Position Data Dictionary Professor Not applicable Latest degree Title and more details about the data/document Medical doctor The study protocol and the informed consent use will be shared after the completion of the study, if requested. Other areas of specialty/work When the data will become available and for how Infectious diseases long Street address Not Applicable Keshavarz Blvd. Gharib St. To whom data/document is available City The documents will be made available to any interested Tehran researcher, affiliated with a university/institution wanting Province to use them. Tehran Under which criteria data/document could be used Postal code There are no specific criteria for use. 1419733141 From where data/document is obtainable Phone Documents can be obtained from the central committee 982161190 of the SOLIDARITY Trial in Iran--Dr. Hossein Poustchi or Email Dr. Minoo Mohraz. [email protected] What processes are involved for a request to access

8 data/document Poustchi. Formal request from the researcher interested, in their Comments affiliated university's letterhead sent to Dr. Hossein

9