Efficacy and Safety of Sirolimus in COVID-19 Infection

NCT04461340 | Unknown Phase 2

• 1 other identifier: sirolimus in COVID 19
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This research is planned to illustrate the efficacy and safety of sirolimus as an adjuvant agent to the standard treatment protocol against COVID-19 infection

Conditions

COVID 19

Keywords

sirolimus; COVID 19

Outcome Measures

Primary Outcomes (2)

• Time to clinical recovery

  The duration from start of treatment to normalization of pyrexia, respiratory rate ,O2 saturation and relief of cough that is maintained for at least 72 hours.

  14-28 days

• Viral clearance

  Two successive negative COVID-19 PCR analysis tests 48-72 hours apart

  14 days

Secondary Outcomes (5)

• radiological lung extension

  14 days

• drug adverse events

  28 days

• 28 day mortality

  28 day

• intensive care unit (ICU) admission rate

  28 days

• Duration of hospital stay

  28 days

Study Arms (2)

Group A

EXPERIMENTAL

20 patients will receive sirolimus ( oral dose of 6 mg on day 1 followed by 2 mg daily for 9 days) plus national standard of care therapy against COVID 19

Drug: Sirolimus

Group B

NO INTERVENTION

20 patients will receive only national standard of care therapy against COVID 19

Interventions

Sirolimus DRUG

oral dose of 6 mg on day1 followed by 2 mg daily for 9 days

Also known as: Rapamune

Group A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (˃18 years) COVID-19 positive patients (confirmed by PCR).
• Moderate infection ( pneumonia ± leucopenia or lymphopenia ).

You may not qualify if:

• Severe or life threatening COVID infection: Severe disease is defined as: dyspnea, respiratory frequency ≥ 30/min, blood oxygen saturation ≤ 93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio \< 300, and/or lung infiltrates \> 50% within 24 to 48 hours. Life threatening disease is defined as: respiratory failure, septic shock, and/or multiple organ dysfunction or failure .
• Pregnant or lactating females.
• Participation in any investigational clinical study, other than observational, within the past 30 days; or plans to participate in such a study at any time from the day of enrollment until 30 days post-treatment in the current study.
• Allergy or hypersensitivity to sirolimus.
• Taking immunosuppressive drugs.
• Glomerular filtration rate (GFR) \< 30 ml/min by CKD-EPI equation.
• liver cirrhosis .
• Decompensated heart failure.
• known active tuberculosis (TB) or history of incompletely treated TB.
• Uncontrolled systemic bacterial or fungal infections.
• Drugs that may affect sirolimus level: antifungals, diltiazem, verapamil, nicardipine, phenytoin, phenobarbital, rifampicin, carbamazepine.

Sponsors & Collaborators

• Alexandria University: lead

Study Sites (1)

Faculty of Medicine, Alexandria university, Egypt

Alexandria, 21526, Egypt

RECRUITING

Related Publications (14)

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb 15;395(10223):514-523. doi: 10.1016/S0140-6736(20)30154-9. Epub 2020 Jan 24.

  PMID: 31986261 BACKGROUND

• Singhal T. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 2020 Apr;87(4):281-286. doi: 10.1007/s12098-020-03263-6. Epub 2020 Mar 13.

  PMID: 32166607 BACKGROUND

• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

  PMID: 32007143 BACKGROUND

• Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available.

  PMID: 32125452 BACKGROUND

• Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.

  PMID: 32217835 BACKGROUND

• Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, Liu ZS. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study. World J Pediatr. 2020 Jun;16(3):251-259. doi: 10.1007/s12519-020-00354-4. Epub 2020 Mar 19.

  PMID: 32193831 BACKGROUND

• Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2.

  PMID: 28466096 BACKGROUND

• Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020 Mar 16;14(1):69-71. doi: 10.5582/bst.2020.01020. Epub 2020 Jan 28.

  PMID: 31996494 BACKGROUND

• Seto B. Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin Transl Med. 2012 Nov 15;1(1):29. doi: 10.1186/2001-1326-1-29.

  PMID: 23369283 BACKGROUND

• Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, Traynor D, Johnson RF, Dyall J, Kuhn JH, Olinger GG, Hensley LE, Jahrling PB. Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob Agents Chemother. 2015 Feb;59(2):1088-99. doi: 10.1128/AAC.03659-14. Epub 2014 Dec 8.

  PMID: 25487801 BACKGROUND

• Wang CH, Chung FT, Lin SM, Huang SY, Chou CL, Lee KY, Lin TY, Kuo HP. Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure. Crit Care Med. 2014 Feb;42(2):313-21. doi: 10.1097/CCM.0b013e3182a2727d.

  PMID: 24105455 BACKGROUND

• Jia X, Liu B, Bao L, Lv Q, Li F, Li H, An Y, Zhang X, Cao B, Wang C. Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration. PLoS Pathog. 2018 Nov 13;14(11):e1007428. doi: 10.1371/journal.ppat.1007428. eCollection 2018 Nov.

  PMID: 30422993 BACKGROUND

• Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14. doi: 10.1038/s41421-020-0153-3. eCollection 2020.

  PMID: 32194980 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Mohamed Mamdouh Elsayed, MD

  lecturer

  PRINCIPAL INVESTIGATOR

• Ayman I Baess, MD

  Associate professor

  STUDY CHAIR

• Heba M El weshahi, MD

  professor

  STUDY CHAIR

• Nermine H Zakaria, MD

  professor

  STUDY CHAIR

Central Study Contacts

Mohamed Mamdouh Elsayed, MD

CONTACT

00201068055103; dr_mohamedmamdouh87@yahoo.com

Ayman I Baess, MD

CONTACT

00201006822068; Ayman.baeis@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: lecturer

Model Details: single-blinded randomized clinical trial in which participants will be randomly assigned to one of the study groups using block randomization with a ratio of 1:1.

Study Record Dates

• First Submitted: July 4, 2020
• First Posted: July 8, 2020
• Study Start: August 15, 2020
• Primary Completion: October 30, 2020
• Study Completion: November 30, 2020
• Last Updated: September 9, 2020

Record last verified: 2020-09

Locations

EG (1)