The Efficacy of Lopinavir Plus Ritonavir and Arbidol Against Novel Coronavirus Infection (ELACOI)

• ClinicalTrials.gov Identifier: NCT04252885
• Recruitment Status: Completed
• First Posted: February 5, 2020
• Last Update Posted: July 1, 2020
• Sponsor: Guangzhou 8th People's Hospital
• Information provided by (Responsible Party): Linghua LI, Guangzhou 8th People's Hospital

Tracking Information

• First Submitted Date: January 30, 2020
• First Posted Date: February 5, 2020
• Last Update Posted Date: July 1, 2020
• Actual Study Start Date: January 28, 2020
• Actual Primary Completion Date: April 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 31, 2020)

The rate of virus inhibition [ Time Frame: Day 0, 2, 4, 7, 10, 14 and 21 ]

Novel coronaviral nucleic acid is measured in nose / throat swab at each time point.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 31, 2020)

• The disease prorogation-temperature [ Time Frame: Day 0 till day 21 ]
  Body temperature will be followed everyday during time frame.
• The disease prorogation-respiratory function 1 [ Time Frame: Day 0 till day 21 ]
  Respiratory rate will be followed everyday during time frame.
• The disease prorogation-respiratory function 2 [ Time Frame: Day 0 till day 21 ]
  Oxygen saturation of blood will be followed everyday during time frame.
• The disease prorogation-respiratory function 3 [ Time Frame: Day 0, 4, 7, 10, 14 and 21 ]
  Chest imaging will be taken at each time point.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 31, 2020)

• Patients health condition-routine test [ Time Frame: Day 0 till day 21 ]
  Blood pressure and heart rate will be followed everyday during time frame.
• Patients health condition-liver function [ Time Frame: Day 0, 4, 7, 10, 14 and 21 ]
  Liver function will be assessed as AST, ALT and TBIL at each time point.
• Patients health condition-kidney function [ Time Frame: Day 0, 4, 7, 10, 14 and 21 ]
  Kidney function will be assessed as eGFR and creatine clearance rate at each time point.
• Patients health condition-other blood routine test [ Time Frame: Day 0, 4, 7, 10, 14 and 21 ]
  Blood routine and myocardial enzyme will be measured at each time point.
• Patients health condition-blood routine test [ Time Frame: Day 0, 4, 7, 10, 14 and 21 ]
  Flow cytometry classification and counting and cytokines will be measured at each time point.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: The Efficacy of Lopinavir Plus Ritonavir and Arbidol Against Novel Coronavirus Infection
• Official Title: A Randomized, Open-label, Controlled Study of the Efficacy of Lopinavir Plus Ritonavir and Arbidol for Treating With Patients With Novel Coronavirus Infection
• Brief Summary: The study explores the efficacy of lopinavir plus ritonavir and arbidol in treating with novel coronavirus infection. As a result this study would provide evidence for the clinical usage of these drugs in the future .
• Detailed Description: This is a phase IV, open-labelled, randomized controlled clinical trial. A total of 125 cases who are novel coronavirus positive are planned to be recruited. These cases are randomized into 3 groups: in group A（Standard treatment+lopinavir/ritonavir）, 50 cases are given ordinary treatment plus a regimen of lopinavir (200mg) and ritonavir (50mg) (oral, q12h, every time 2 tablets of each, taking for 7-14 days). In group B（Standard treatment+arbidol） , 50 cases are given ordinary treatment plus a regimen of arbidol (100mg) (oral, tid, 200mg each time, taking for 7-14 days). In group C（Standard treatment）, 25 cases are only given ordinary treatment. The observation duration is 21 days. Patients will be followed up at baseline (day 0) and day 2, 4, 7, 10,14, 21 after receiving indicated treatment. The primary observed indicators include viral nucleic in acid nose / throat swab, body temperature, respiratory rate, oxygen saturation of blood, chest imaging. The secondary observed indicators include but not limited to blood pressure, heart rate, blood routine test, liver and kidney function, myocardial enzyme, flow cytometry classification and counting, cytokines, other infection indicators, conditions and parameters of auxiliary respiration, the total days in hospital, exacerbation and mortality.
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

125 patients are randomized in 3 groups (2:2:1). In group A(Standard treatment+lopinavir/ritonavir) , 50 cases are given ordinary treatment plus a regimen of lopinavir (200mg) and ritonavir (50mg) (oral, q12h, every time 2 tablets of each, taking for 7-14 days). In group B (Standard treatment+arbidol), 50 cases are given ordinary treatment plus a regimen of arbidol (100mg) (oral, tid, 200mg each time, taking for 7-14 days). In group C (Standard treatment）, 25 cases are only given ordinary treatment.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Coronavirus Infections

Intervention

• Drug: Lopinavir and Ritonavir Tablets
  As indicated in arm/group descriptions
  Other Name: Kletra
• Drug: Arbidol
  As indicated in arm/group descriptions

Study Arms

• Experimental: Group A-Standard treatment+lopinavir/ritonavir
  In group A, 50 cases are given ordinary treatment plus a regimen of lopinavir (200mg) and ritonavir (50mg) (oral, q12h, every time 2 tablets of each, taking for 7-14 days).
  Intervention: Drug: Lopinavir and Ritonavir Tablets
• Active Comparator: Group B-Standard treatment+arbidol
  In group B, 50 cases are given ordinary treatment plus a regimen of arbidol (100mg) (oral, tid, 200mg each time, taking for 7-14 days).
  Intervention: Drug: Arbidol
• No Intervention: Group C-Standard treatment
  In group C, 25 cases are only given ordinary treatment.

• Publications *: Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y, Mo X, Wang J, Wang Y, Peng P, Chen X, Hong W, Xiao G, Liu J, Zhang L, Hu F, Li F, Zhang F, Deng X, Li L. Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial. Med (N Y). 2020 Dec 18;1(1):105-113.e4. doi: 10.1016/j.medj.2020.04.001. Epub 2020 May 19.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 29, 2020): 86
• Original Estimated Enrollment (submitted: January 31, 2020): 125
• Actual Study Completion Date: May 31, 2020
• Actual Primary Completion Date: April 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• In sputum, throat swab, lower respiratory tract secretion, blood and other samples, the nucleic acid of the novel coronavirus was positive, or the sequencing of the virus gene was highly homologous with the known novel coronavirus
• Age is between 18-80 years old, the weight is more than 30kg, and there is no limit for men and women
• The following conditions were met: creatinine ≤ 110 umol / L, creatinine clearance rate (EGFR) ≥ 60 ml / min / 1.73m2, AST and ALT ≤ 5 × ULN, TBIL ≤ 2 × ULN;
• The subjects should fully understand the purpose, nature, method and possible reaction of the study, voluntarily participate in the study and sign the informed consent.

Exclusion Criteria:

• Have a clear history of lopinavir or ritonavir or arbidol allergy
• Severe nausea, vomiting, diarrhea and other clinical manifestations affect the oral or absorption of the drugs
• At the same time, take drugs that may interact with lopinavir or ritonavir or arbidol
• Patients with serious underlying diseases, including but not limited to heart disease (including history of angina pectoris or coronary heart disease or myocardial infarction, atrioventricular block), lung, kidney, liver malfunction and mental diseases that cannot be treated together
• ancreatitis or hemophilia
• Pregnant and lactating women
• Suspected or confirmed history of alcohol and drug abuse
• Participated in other drug trials in the past month
• The researchers judged that patients were not suitable for the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04252885
• Other Study ID Numbers: GZ8H-V1.0 20200122
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Linghua LI, Guangzhou 8th People's Hospital
• Study Sponsor: Guangzhou 8th People's Hospital
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Guangzhou 8th People's Hospital
• Verification Date: June 2020