This phase II trial identifies the effect of N-acetylcysteine in treating patients who have severe coronavirus disease-2019 (COVID-19) infection that does not respond to treatment (refractory) and are either patients in a critical care unit and/or are connected to a ventilator, or who are not in a critical care unit but require large amounts of supplemental oxygen. Recent studies suggest that the virus that causes COVID-19 may work by suppressing the immune system, which is the body's defense against infections and other diseases. White blood cells called lymphocytes are an important part of this defense, but recently it was found that the number of lymphocytes in a COVID-19 patient’s blood goes down as the infection gets worse and goes up as a patient gets better. N-acetylcysteine has been shown to help increase the number of lymphocytes in the blood when a virus is responsible for lowering it. This trial may help researchers determine whether N-acetylcysteine is effective enough against the virus that causes COVID-19 such that patients could leave the critical care unit or be taken off a ventilator, or could be prevented from needing ventilator support and management in a critical care unit.
Additional locations may be listed on ClinicalTrials.gov for NCT04374461.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. Estimate the clinical success rate (defined as not requiring critical-care unit level care or mechanical ventilation) with acetylcysteine (N-acetylcysteine) in intensive care unit (ICU) patients with COVID-19 infection.
SECONDARY OBJECTIVES:
I. Evaluate toxicity associated with N-acetylcysteine in COVID-19 infection.
II. Estimate the time of mechanical ventilation required with N-acetylcysteine in COVID-19 infection in mechanically ventilated patients.
III. Estimate the supplementary oxygen requirements with N-acetylcysteine in COVID-19 infection in non-mechanically ventilated patients.
IV. Evaluate for markers of sensitivity and characterize the effects of N-acetylcysteine treatment through the following:
IVa. Lymphocyte counts and subset analysis, including naive/effector/memory/regulatory T-cell differentiation and exhaustion markers, as well as B-cell counts obtained on day 1 (D1), weekly, and at end of treatment.
IVb. Serum cytokines and acute phase reactants known to be increased in severe COVID19 infections, including IL-6, ferritin, C-reactive protein, LDH, D-dimer, procalcitonin obtained on D1, weekly, and at end of treatment.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM A: Mechanically ventilated and/or critical-care unit patients receive N-acetylcysteine intravenously (IV) over 24 hours daily for up to 3 weeks in the absence of unacceptable toxicity, death, transfer out of the critical care unit, or extubation. Patients may restart treatment if Arm B eligibility criteria are met. Patients also receive other COVID-19 directed treatments at the discretion of the treating physician.
ARM B: Non-mechanically ventilated, non-critical care unit patients requiring supplemental oxygen of 2 liters (L) or more by nasal cannula receive N-acetylcysteine IV over 24 hours daily for up to 3 weeks in the absence of unacceptable toxicity, death, discharge from hospital, admission to a critical care unit, or intubation. Patients may restart treatment if Arm A eligibility criteria are met. Patients also receive other COVID-19 directed treatments at the discretion of the treating physician.
After completion of study treatment, patients are followed weekly for 30 days.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorSantosha A. Vardhana
