Clinical trial NCT04560231: Remdesivir in COVID-19 Lahore General Hospital
Official title: Is Remdesivir a Possible Therapeutic Option for SARS-CoV-2 : An Interventional Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: SARS-CoV Infection
Keywords: COVID-19
Remdesivir
Lead sponsor: Lahore General Hospital
Sponsor class: OTHER_GOV
First posted: 2020-09-23
Enrollment: 30
Sex: ALL
Minimum age (years): 15
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Qausi-experimental
Primary purpose: TREATMENT

Brief summary: Remdesivir is a monophosphoramidate prodrug of an adenosine analogue and it has a broad-spectrum antiviral activity against paramyxoviruses, falviviruses and coronaviruses. It showed in vitro activity on human airway epithelial cells against SARS-CoV-2. It is an investigational drug and granted an Emergency Use Authorization by Food and Drug Administration FDA, so it is under clinical trial.

The potent mechanism of action of this drug is still unclear but it effects through several processes. It can interfere with nsp12 polymerase even when exoribonuclease proofreading is intact. It can also produce nucleoside triphosphate NTP that acts pharmacologically active alternate substrate of RNA-chain terminator, as a result NTP can constrain active triphosphates into viral RNA of coronaviruses. There is evidence of high genetic barrier to develop resistance against Remdesivir in coronavirus as a result of which is maintains its effectiveness in antiviral therapies against these viruses. Effectiveness of Remdesivir has been reported against different groups of coronaviruses including Alphacoronavirus NL63 and several SARS/MERS-CoV coronaviruses.

Detailed description: This is interventional single-center study, that will be done at Lahore General Hospital in which 95 beds are allocated for COVID-19 patients including ICUs and HDUs. Ethical approval will be obtained from research ethical committee of Lahore General hospital, Lahore. Informed consent will be obtained from all patients who will agree to publish their data in this research. Patient's privacy protection will be obeyed with the Helsinki Declaration.

The aim of this study is to evaluate clinical effectiveness of this investigational drug, started a clinical trial of this drug on laboratory-confirmed COVID-19 patients at a tertiary care hospital of Lahore, Pakistan.

Eligibility criteria: Inclusion Criteria:

* All patients of all ages, males, and females who will be diagnosed COVID-19 positive by RT-PCR with moderate illness.
* Patients having classical radiological lesions of COVID-19 on X-ray chest or HRCT chest.
* Respiratory rate \> 22/ min and \>50% of radiological involvement of lung with typical lesions.
* FiO2 remain static or improving along with \> 30% deranged ≥ 2 biochemical markers CRP \> 20 mg/l, LDH \> 600 U/L, D.Dimer \> 0.5mg/l or 500 ng/ml, Serum Ferritin \< 500 ng/ml or mcg/l will be included in clinical trial.

Exclusion Criteria:

* Patients on Invasive mechanical ventilation (IMV).
* Patients with respiratory rate \< 20/mins and whose laboratory findings will not be deranged \> 20%.
* Presences of chronic renal failure \> 4 stage, GFR \< 30ml/min/1.73m2.
* ALT/AST \> 5 times than normal values.
* Pregnant women.

Primary outcomes:
measure: Clinical response after administration
timeFrame: 10 days
Secondary outcomes:
measure: Clinical response to treatment
timeFrame: 15 days
measure: Duration of hospitalization
timeFrame: 15 days
measure: Supplemental Oxygen Requirement from Baseline
timeFrame: 15 days
Other outcomes:
Locations:
city: Lahore
country: Pakistan
facility: Muhammad Irfan Malik
state: Punjab
Study officials:
affiliation: Post-Graduate Medical Institute, Lahore General Hospital, Lahore Pakistan
name: Muhammad Irfan Malik, FCPS
role: STUDY_DIRECTOR
References:
citation: Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, Fu S, Gao L, Cheng Z, Lu Q, Hu Y, Luo G, Wang K, Lu Y, Li H, Wang S, Ruan S, Yang C, Mei C, Wang Y, Ding D, Wu F, Tang X, Ye X, Ye Y, Liu B, Yang J, Yin W, Wang A, Fan G, Zhou F, Liu Z, Gu X, Xu J, Shang L, Zhang Y, Cao L, Guo T, Wan Y, Qin H, Jiang Y, Jaki T, Hayden FG, Horby PW, Cao B, Wang C. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May 16;395(10236):1569-1578. doi: 10.1016/S0140-6736(20)31022-9. Epub 2020 Apr 29.
citation: Davies M, Osborne V, Lane S, Roy D, Dhanda S, Evans A, Shakir S. Remdesivir in Treatment of COVID-19: A Systematic Benefit-Risk Assessment. Drug Saf. 2020 Jul;43(7):645-656. doi: 10.1007/s40264-020-00952-1.
citation: Li Z, Wang X, Cao D, Sun R, Li C, Li G. Rapid review for the anti-coronavirus effect of remdesivir. Drug Discov Ther. 2020;14(2):73-76. doi: 10.5582/ddt.2020.01015.