ICMR researchers release protocol for administering Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India:

New Delhi: With the Central Drugs Standard Control Organization approving, the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country, a recent report in the Indian Journal of Medical Research, the official journal of apex research body, Indian Council of Medical Research (ICMR) has now released the Protocol for restricted public health emergency use of Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India.

The protocol which has been prepared by the researchers of ICMR and AIIMS notes that this protocol is to be implemented along with the WHO guidelines on clinical management of severe acute respiratory infection when nCoV infection is suspected: Interim Guidance

Following are some of the details of the protocol

Patient eligibility criteria

Inclusion criteria: Include

(1) Adult over 18 yr of age;

(2) Laboratory confirmation of COVID-19 infection by real-time reverse transcription-polymerase chain reaction (qRT-PCR) from the recommended sample

(3)Symptomatic patients with any one of the following: (i) Respiratory distress with respiratory rate ≥22/min or SpO2 of <94 per cent, (ii) Lung parenchymal infiltrates on chest X-ray or CT scan, (iii) Hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication, (iv) New-onset organ dysfunction (one or more of the following): (a) Increase in creatinine by 50 per cent from baseline, glomerular filtration rate (GFR) reduction by >25 per cent from baseline or urine output of <0.5 ml/kg for six hours, (b) Reduction of Glasgow Coma Scale (GCS) score by two or more, and (c) Any other organ dysfunction; (v) High-risk groups with age >60 yr, and those with hypertension, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons; (vi) Informed consent from patient and caretaker. Consent from legally authorized representative in case the patient is not able to provide the same due to his/her medical condition.

Exclusion criteria:(i) A patient with hepatic impairment [Child Pugh C or alanine aminotransferase (ALT) over 5X the upper limit of normal]; (ii) Use of medications that are contraindicated with lopinavir/ritonavir and that cannot be replaced or stopped, e.g., rifampicin, benzodiazepines, simvastatin, voriconazole and sildenafil; and (iii) Known HIV-infected individual receiving other protease inhibitors containing regimens that cannot be replaced by lopinavir/ritonavir.

Dosage of lopinavir/ritonavir: (i) Lopinavir/ritonavir 200 mg/50 mg - two tablets every 12 h for 14 days or for seven days after becoming asymptomatic, whichever is earlier; and (ii)For patients who are unable to take medications by mouth, 400 mg lopinavir /100 mg ritonavir 5 ml suspension every 12 h for 14 days or seven days after becoming asymptomatic whichever is earlier, via a nasogastric tube.

Baseline laboratory investigations:

(i) Haemogram; (ii)Liver function tests (LFTs); (iii) Renal function tests (RFTs); (iv) Haemoglobin A1c and blood sugar, if required; (v) RT-PCR for SARS-CoV-2 (respiratory samples: nasopharyngeal swab, oropharyngeal swab, in addition, sputum, bronchoalveolar lavage (BAL), if available); (vi) PT/international normalized ratio, electrolytes, arterial blood gas; (vii) Lipid profile; (viii) Chest X-ray; (ix) Electrocardiogram (ECG); (x) Hepatitis B and C; and (xi) Other investigations as deemed appropriate by the treating physician.

Laboratory sample collection (other than investigations for routine clinical monitoring): (i)Oropharyngeal swabs (every third day) - for SARS-CoV-2 RT-PCR (samples to be transported to ICMR-National Institute of Virology, Pune, as per the guidelines); (ii) Blood sample (every week) - Haemogram, LFT (alternate days), RFT and electrolytes (to monitor drug-induced adverse events); (iii) ECG; and (iv) Other investigations as deemed appropriate by the treating physician.

All samples would be stored for future-related tests.

Frequency and duration of monitoring: (i) Patients should be monitored daily until discharge from the hospital and followed up till 90 days; and (ii) Patient should be discharged on clinical recovery and after obtaining two consecutive negative RT-PCR results at least 24 h apart from oropharyngeal swabs (to demonstrate viral clearance).

Outcome assessment

Clinical outcomes: (i)Hospital length of stay; (ii) Intensive care unit (ICU)-free days; (iii) Requiring use of ventilator; (iv) Mortality in the ICU; (v) Mortality in the hospital; and (vi) Mortality at 14, 28 and 90 days.

Safety outcomes: (i) Acute pancreatitis (defined as having: (a) abdominal pain radiating to the back; (b) serum amylase at least three times greater than the upper limit of normal; (c) radiological evidence, such as contrast CT/magnetic resonance imaging/ultrasonography, of acute pancreatitis); (ii) Elevation of ALT to more than five-fold upper normal limit; (iii) Anaphylaxis; and (iv) Adverse events and serious adverse events.

Laboratory outcomes: (i) Viral RNA loads and cycle threshold values in serial samples of nasopharyngeal and oropharyngeal swabs and blood, collected every third day (to document viral replication kinetics).

You can read the full protocol by Clicking on the following link

Bhatnagar T, Murhekar MV, Soneja M, Gupta N, Giri S, Wig N, Gangakhedkar R. Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India: Protocol for restricted public health emergency use. Indian J Med Res [serial online] 2020 [cited 2020 Apr 29];151:184-9. Available from: http://www.ijmr.org.in/text.asp?2020/151/2/184/280484

For more details click on the link: http://www.ijmr.org.in/text.asp?2020/151/2/184/280484