A Study of N-acetylcysteine in Patients With COVID-19 Infection

Study Overview
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Brief Summary
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The study researchers think that a medication called N-acetylcysteine can help fight the COVID-19 virus by boosting a type of cell in your immune system that attacks infections. By helping your immune system fight the virus, the researchers think that the infection will get better, which could allow the patient to be moved out of the critical care unit or go off a ventilator, or prevent them from moving into a critical care unit or going on a ventilator. The US Food and Drug Administration (FDA) has approved N-acetylcysteine to treat the liver side effects resulting from an overdose of the anti-inflammatory medication Tylenol® (acetaminophen). N-acetylcysteine is also used to loosen the thick mucus in the lungs of people with cystic fibrosis or chronic obstructive pulmonary disease (COPD). This study is the first to test N-acetylcysteine in people with severe COVID-19 infections.

Official Title
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Phase II Study of N-acetylcysteine in Severe or Critically Ill Patients With Refractory COVID-19 Infection

Conditions
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Covid-19

Intervention / Treatment
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* Drug: N-acetylcysteine
* Other: Peripheral Blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented COVID-19 infection (either performed on site or documented external report) Age ≥ 18 Arm A: Admission to an intensive care unit at MSK (M-11) and/or receiving mechanical ventilation Absolute lymphocyte count ≤ 1.0/mm3 As the 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: Arm B:Requiring 2L or more of supplemental oxygen by nasal cannula or higher to maintain SpO2 of 95% Exclusion Criteria: Arm B: requiring mechanical ventilation or admission to an intensive care unit at MSK (M11)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a single-institution study that will be open at MSKCC's Manhattan campus. Patients will be enrolled into 2 separate arms. The mechanically ventilated &/or managed in a critical-care arm is closed to accrual as of September 2020.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mechanically ventilated &/or managed in a critical-care<br>This arm is closed to accrual as of September 2020. Patients in both arms will receive N-acetylcysteine IV 6 g/day in addition to supportive and/or COVID-19 directed treatments at the discretion of the treating physician. Patients will receive treatment for a maximum of 3 weeks or until one of the following: Arm A: Transfer out of the critical-care unit Extubation Toxicity Death | Drug: N-acetylcysteine<br>* Patients in both arms will receive N-acetylcysteine IV 6 g/day in addition to supportive and/or COVID-19 directed treatments at the discretion of the treating physician. Treatment interruptions for up to 48 hours are permissible if there is a clinical indication to hold the study drug. Patients can restart drug if they have been off drug for less than 48 hours. Patients are also eligible to restart N-acetylcysteine treatment on the same treatment arm without reconsent if they are within the 30 day followup period after their prior course of treatment on this protocol.<br>Other: Peripheral Blood<br>* A total of 16mL of research whole blood will be collected in CPT tubes at baseline, Cycle 2 Day 1 (or as close as feasible, when still coordinating sample collection across patients in a critical-care unit), and at end of study.<br>|
| Experimental: non-mechanically ventilated, non-critical-care<br>Patients in both arms will receive N-acetylcysteine IV 6 g/day in addition to supportive and/or COVID-19 directed treatments at the discretion of the treating physician. Patients will receive treatment for a maximum of 3 weeks or until one of the following: Arm B: Discharge from hospital Admission to a critical-care unit Intubation Toxicity Death | Drug: N-acetylcysteine<br>* Patients in both arms will receive N-acetylcysteine IV 6 g/day in addition to supportive and/or COVID-19 directed treatments at the discretion of the treating physician. Treatment interruptions for up to 48 hours are permissible if there is a clinical indication to hold the study drug. Patients can restart drug if they have been off drug for less than 48 hours. Patients are also eligible to restart N-acetylcysteine treatment on the same treatment arm without reconsent if they are within the 30 day followup period after their prior course of treatment on this protocol.<br>Other: Peripheral Blood<br>* A total of 16mL of research whole blood will be collected in CPT tubes at baseline, Cycle 2 Day 1 (or as close as feasible, when still coordinating sample collection across patients in a critical-care unit), and at end of study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arm A: number of patients who are successfully extubated and/or transferred out of critical care due to clinical improvement |  | 1 year | 
| Arm B: number of patients who are discharged from the hospital due to clinical improvement |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-acetylcysteine, 20-168