A Study of N-acetylcysteine in Patients with COVID19 Infection

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.

Inclusion Criteria

• Documented COVID-19 infection (either performed on site or documented external report)
• Arm A: * Admission to an intensive care unit at Memorial Sloan Kettering (MSK) (M-11) and/or receiving mechanical ventilation * Absolute lymphocyte count =< 1.0/mm^3 ** As the absolute lymphocyte count (ALC) of patients with lymphoid malignancies is unreliable, they may be enrolled at the discretion of the treating physician after review of their blood work
• Arm B: * Requiring 2L or more of supplemental oxygen by nasal cannula or higher to maintain blood oxygen saturation level (SpO2) of 95%
• NOTE: The concurrent use of COVID-19 directed anti-viral therapies or other immunomodulatory therapies including steroids or tocilizumab directed at treating either COVID-19 infection or COVID-19-related inflammatory responses is permitted on this study
• NOTE: Patients who receive treatment on Arm A and are subsequently transferred out of the ICU will remain eligible for Arm B; patients who receive treatment on Arm B and are subsequently admitted to the ICU will remain eligible for Arm A

Exclusion Criteria

• Arm B: Requiring mechanical ventilation or admission to an intensive care unit at MSK (M11)

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.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Santosha A. Vardhana

• Primary ID 20-168
• Secondary IDs NCI-2020-03373
• Clinicaltrials.gov ID NCT04374461