Application of Desferal to Treat COVID-19

Application of Iron Chelator (Desferal) to Reduce the Severity of COVID-19 Manifestations

In this study, defined cases of COVID-19 with mild, moderate or severe pneumonia will be treated with standard treatment regimens in combination with IV injection of Deferoxamine. Improvement in clinical, laboratory and radiological manifestations will be evaluated in treated patient compared to control group.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Deferoxamine

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Kermanshah, Iran, Islamic Republic of, 083
    • Recruiting
    • Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
    • Contact: Yadollah Shakiba, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Clinical diagnosis of COVID-19 Disease,

Exclusion Criteria:

Previous history of allergy to Deferoxamin, Pregnancy, kidney dysfunction,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Desferal addition to standard treatment	Drug: Deferoxamine; Intravenous infusion of Deferoxamine
Experimental: Experimental: standard treatment	Drug: Deferoxamine; Intravenous infusion of Deferoxamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate	All cause of death	up to 20 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in patients clinical manifestation	Mild, Moderate or Severe	up to 20 days
change in patients PaO2		up to 20 days
Length of hospitalization	days	up to 20 days
C-reactive protein		up to 20 days
lymphocyte count		up to 20 days
length of intensive care unit stay		1 to 20 days

Collaborators and Investigators

• Sponsor: Kermanshah University of Medical Sciences
• Investigators: Study Director: Yadollah Shakiba, MD, PhD, Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Principal Investigator: Amir Kiani, PhD, Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

Publications and helpful links

General Publications

• Drakesmith H, Prentice A. Viral infection and iron metabolism. Nat Rev Microbiol. 2008 Jul;6(7):541-52. doi: 10.1038/nrmicro1930.
• Nairz M, Haschka D, Demetz E, Weiss G. Iron at the interface of immunity and infection. Front Pharmacol. 2014 Jul 16;5:152. doi: 10.3389/fphar.2014.00152. eCollection 2014.
• Georgiou NA, van der Bruggen T, Oudshoorn M, Nottet HS, Marx JJ, van Asbeck BS. Inhibition of human immunodeficiency virus type 1 replication in human mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and bleomycin. J Infect Dis. 2000 Feb;181(2):484-90. doi: 10.1086/315223.
• Vlahakos D, Arkadopoulos N, Kostopanagiotou G, Siasiakou S, Kaklamanis L, Degiannis D, Demonakou M, Smyrniotis V. Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs. Artif Organs. 2012 Apr;36(4):400-8. doi: 10.1111/j.1525-1594.2011.01385.x. Epub 2011 Dec 21.
• Wang H, Li Z, Niu J, Xu Y, Ma L, Lu A, Wang X, Qian Z, Huang Z, Jin X, Leng Q, Wang J, Zhong J, Sun B, Meng G. Antiviral effects of ferric ammonium citrate. Cell Discov. 2018 Mar 27;4:14. doi: 10.1038/s41421-018-0013-6. eCollection 2018.
• Cinatl J Jr, Cinatl J, Rabenau H, Gumbel HO, Kornhuber B, Doerr HW. In vitro inhibition of human cytomegalovirus replication by desferrioxamine. Antiviral Res. 1994 Sep;25(1):73-7. doi: 10.1016/0166-3542(94)90095-7.
• Visseren F, Verkerk MS, van der Bruggen T, Marx JJ, van Asbeck BS, Diepersloot RJ. Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A. Eur J Clin Invest. 2002 Mar;32 Suppl 1:84-90. doi: 10.1046/j.1365-2362.2002.0320s1084.x.
• Sappey C, Boelaert JR, Legrand-Poels S, Forceille C, Favier A, Piette J. Iron chelation decreases NF-kappa B and HIV type 1 activation due to oxidative stress. AIDS Res Hum Retroviruses. 1995 Sep;11(9):1049-61. doi: 10.1089/aid.1995.11.1049.
• Chang HC, Bayeva M, Taiwo B, Palella FJ Jr, Hope TJ, Ardehali H. Short communication: high cellular iron levels are associated with increased HIV infection and replication. AIDS Res Hum Retroviruses. 2015 Mar;31(3):305-12. doi: 10.1089/aid.2014.0169. Epub 2014 Oct 7.
• Meyer D. Iron chelation as therapy for HIV and Mycobacterium tuberculosis co-infection under conditions of iron overload. Curr Pharm Des. 2006;12(16):1943-7. doi: 10.2174/138161206777442164.
• Cinatl J, Scholz M, Weber B, Cinatl J, Rabenau H, Markus BH, Encke A, Doerr HW. Effects of desferrioxamine on human cytomegalovirus replication and expression of HLA antigens and adhesion molecules in human vascular endothelial cells. Transpl Immunol. 1995 Dec;3(4):313-20. doi: 10.1016/0966-3274(95)80017-4.
• Mabeza GF, Loyevsky M, Gordeuk VR, Weiss G. Iron chelation therapy for malaria: a review. Pharmacol Ther. 1999 Jan;81(1):53-75. doi: 10.1016/s0163-7258(98)00037-0.
• Weinberg GA. Iron chelators as therapeutic agents against Pneumocystis carinii. Antimicrob Agents Chemother. 1994 May;38(5):997-1003. doi: 10.1128/AAC.38.5.997.
• Paradkar PN, De Domenico I, Durchfort N, Zohn I, Kaplan J, Ward DM. Iron depletion limits intracellular bacterial growth in macrophages. Blood. 2008 Aug 1;112(3):866-74. doi: 10.1182/blood-2007-12-126854. Epub 2008 Mar 27.
• Giannakopoulou E, Pardali V, Zoidis G. Metal-chelating agents against viruses and parasites. Future Med Chem. 2018 Jun 1;10(11):1283-1285. doi: 10.4155/fmc-2018-0100. Epub 2018 May 3. No abstract available.
• Gordeuk V, Thuma P, Brittenham G, McLaren C, Parry D, Backenstose A, Biemba G, Msiska R, Holmes L, McKinley E, et al. Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria. N Engl J Med. 1992 Nov 19;327(21):1473-7. doi: 10.1056/NEJM199211193272101.
• Duchemin JB, Paradkar PN. Iron availability affects West Nile virus infection in its mosquito vector. Virol J. 2017 Jun 5;14(1):103. doi: 10.1186/s12985-017-0770-0.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2020
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 3, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2020
• Last Update Submitted That Met QC Criteria: April 30, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19, Deferoxamine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Siderophores; Deferoxamine
• Other Study ID Numbers: 1398.1224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No