Clinical Scenario:

AB 45-year-old male brought to ER due to difficulty of breathing accompanied by productive cough with
whitish phlegm of 4 days duration and fever with highest Temperature of 38C. Patient denies chest pain, palpitations,
diaphoresis nor LBM. No travel history nor exposure to symptomatic individuals. He is a 10 pack year smoker,
occasional alcoholic drinker, and a software engineer.

At the ER, patient seen awake, coherent and speaks in phrases. Vital signs are as follows: BP 120/70 HR 115
RR 28 Temp 38.9C O2 saturations 94%. COVID swab test was done and was admitted as a case of COVID probable
CAP-MR. Chest x-ray was done and revealed right and left lower lobe pneumonia. Initial read of the Chest HRCT
revealed: bilateral lower lobe pneumonia with note of ground glass opacities right greater than the left.

Patient was given O2 supplementation via nasal cannula at 1-2 LPM with 98% O2sat. He was started with
Ceftriaxone 2g IV OD, and Azithromycin 500mg OD x 5 days.

After 3 days patient tested positive for COVID-19, patient then was started on Lopinavir/Ritonavir
200mg/50mg BID x 10days.

Clinical Question:
Is Lopinavir/Ritonavir compared to standard care regimen effective in accelerating decrease need for O2
supplementation in Covid-19 positive adult patients?

Citation:
https://www.nejm.org/doi/pdf/10.1056/NEJMoa2001282?articleTools=true

Directness
RESEARCH CLINICAL
POPULATION Male and nonpregnant female 45-year-old male COVID-19 positive
patients 18 years of age or older
were eligible if they had a diagnostic
specimen that was positive on RT-
PCR, had pneumonia confirmed by
chest imaging, and had an oxygen
saturation (Sao2) of 94% or less
while they were breathing ambient
air or a ratio of the partial pressure
of oxygen (Pao2) to the fraction of
inspired oxygen (Fio2) (Pao2:Fio2)
at or below 300 mg Hg.
INTERVENTION Lopinavir/Ritonavir 400mg/100mg Lopinavir/Ritonavir 200mg/50mg
BID x 14 days BID x 10 days
COMPARISION Standard of Care(necessary, Standard of care(necessary,
supplemental oxygen, noninvasive supplemental oxygen, noninvasive
and invasive ventilation, antibiotic and invasive ventilation, antibiotic
agents, vasopressor support, renal- agents, vasopressor support, renal-
replacement therapy, and replacement therapy)
extracorporeal membrane oxygen-
ation (ECMO))
OUTCOME time to clinical improvement (the Lopinavir–Ritonavir treatment would
time from randomization to either an accelerate clinical improvement
improvement of 2 points on a 7 (i.e.: Hospitalized but not requiring
 category ordinal scale or discharge supplemental oxygen and/or
from hospital) discharged from hospital)
METHOD open-label, individually randomized, Randomized Controlled clinical
controlled trial trials

Validity
Were patients randomly assigned to treatment groups?
Was allocation concealed?
Were baseline characteristics similar at the start?
Were patients blinded to treatment assignment?
Were caregivers blinded to treatment assignment?
Were outcome assessors blinded to treatment
assignment
Were all patients analysed in the groups to which they
were originally randomized?
Was follow-up rate adequate?
Yes. Page 2 Column 2 Paragraph 1
Yes. Page 3 Column 1 Paragraph 1
Yes. Page 6 Table 1
No. Page 10 Column 2 Paragraph 2
No. Page 10 Column 2 Paragraph 2
No. Page 10 Column 2 Paragraph 2
Yes. Page 4 Column 2 Paragraph 4
Yes. Page 10 column 2 Paragraph 2

Results
Lopinavir/Ritonavir Standard care RR RRR ARR NNT
n/N=rt n/N=rc 95% CI 95% CI Rc-Rt 1/ARR
Rt/Rc Rc-Rt/Rc
Clinical 78/99 70/100 1.12554 0.11115 0.08787 11.37931
improvement
after 28 days CI: 0.95
P=0.21

Applicablity Issues
Sex None
Co-Morbidities None
Race None
Age None
Pathology None

Author’s Conclusion:
In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir/ritonavir treatment
beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a
treatment benefit.

Reviewer’s Conclusion:
We therefore conclude that Lopinavir–Ritonavir treatment has no additional benefit or did not significantly
accelerated clinical improvement due to lack of blinding and small sample sizes.

In our case wherein we classified our patient at low risk category, the study also lacks data on the lopinavir
exposure levels on seriously and critically ill patients.

In order to determine the efficacy and safety of LPVr for COVID-19, we conclude that more adequately
powered randomised clinical trials of LPVr for COVID-19 are required and ideally these studies should be double-
blinded to prevent any form of bias.
Clinical Bottomline:  
Due to limitations and results of the study, we will not use lopinavir/ritonavir in our patients.

Name:
Licup, Karl Sedfrey G.
Rodriguez, Ivory Jo
Date: May 1, 2020