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

• ClinicalTrials.gov Identifier: NCT04374461
• Recruitment Status: Active, not recruiting
• First Posted: May 5, 2020
• Last Update Posted: July 26, 2022
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Covid-19	Drug: N-acetylcysteine; Other: Peripheral Blood	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Treatment
• Official Title: Phase II Study of N-acetylcysteine in Severe or Critically Ill Patients With Refractory COVID-19 Infection
• Actual Study Start Date: May 1, 2020
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: mechanically ventilated &/or managed in a critical-care; 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; 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.; Other: Peripheral Blood; 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.
Experimental: non-mechanically ventilated, non-critical-care; 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; 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.; Other: Peripheral Blood; 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.

Outcome Measures

Primary Outcome Measures :

1. Arm A: number of patients who are successfully extubated and/or transferred out of critical care due to clinical improvement [ Time Frame: 1 year ]
2. Arm B: number of patients who are discharged from the hospital due to clinical improvement [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Santosha Vardhana, MD, PhD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT04374461
• Other Study ID Numbers: 20-168
• First Posted: May 5, 2020
• Last Update Posted: July 26, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Memorial Sloan Kettering Cancer Center:

N-acetylcysteine; 20-168

Additional relevant MeSH terms:

COVID-19; Acetylcysteine; N-monoacetylcystine; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Antiviral Agents; Anti-Infective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antidotes