N-acetylcysteine for COVID-19

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Mechanical ventilation, ICU admission, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether N-acetylcysteine (NAC, also known as Mucomyst, N-A-C Sustain, Acys-5, or Parvolex) can help the immune system combat COVID-19. The goal is to determine if the medication can improve the condition of those with severe COVID-19, potentially enabling them to leave critical care or avoid ventilator use. The trial includes two groups: one for patients already in critical care and another for those needing extra oxygen but not yet in intensive care. Individuals with COVID-19 who require oxygen support or are in critical care might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that N-acetylcysteine (NAC) is generally safe and well-tolerated. This is significant because the FDA has approved NAC for other uses, such as treating liver damage from excessive Tylenol® (acetaminophen) and clearing thick mucus in lung conditions like cystic fibrosis and COPD.

While studies on NAC for COVID-19 continue, its use in other conditions suggests safety. Previous patients have not reported major safety concerns, which is encouraging for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COVID-19?

Unlike the standard COVID-19 treatments that typically focus on antiviral medications or steroids, N-acetylcysteine (NAC) offers a different approach by targeting oxidative stress and inflammation. NAC is an antioxidant that helps replenish glutathione levels, which may protect cells and tissues from damage, especially in severe cases where the lungs are under stress. Researchers are excited about NAC because of its potential to improve outcomes for both critically and non-critically ill patients with COVID-19, possibly offering a new adjunct to existing therapies by enhancing the body's natural defenses.

What evidence suggests that N-acetylcysteine might be an effective treatment for COVID-19?

Research has shown that N-acetylcysteine (NAC) might improve outcomes for COVID-19 patients. Some studies found that NAC can lower inflammation markers, such as C-reactive protein and D-dimer levels, which often rise in severe COVID-19 cases. One review of several studies suggested that NAC might reduce the severity and death rates in COVID-19 patients. However, other studies found no significant improvement in COVID-19 outcomes with NAC, so the evidence remains mixed. In this trial, participants in both treatment arms will receive NAC, as researchers investigate whether it can strengthen the immune system to fight the virus more effectively. ^{1 2 3 6 7}

Who Is on the Research Team?

Santosha Vardhana, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with COVID-19 needing oxygen support to maintain good blood oxygen levels. They must be in intensive care or on a ventilator at MSK (M-11) and have low counts of certain immune cells. People already on mechanical ventilation or admitted to ICU at MSK (M11) can't join.

Inclusion Criteria

You have tested positive for COVID-19.

I need extra oxygen to keep my oxygen levels normal.

Patients with certain types of blood cancers may be allowed to join the study after their doctor reviews their blood test results.

Exclusion Criteria

You need a machine to help you breathe or have to stay in a special hospital unit at MSK.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive N-acetylcysteine IV 6 g/day for a maximum of 3 weeks or until specific clinical endpoints are met

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N-acetylcysteine

Trial Overview Researchers are testing N-acetylcysteine, which may boost the immune system's ability to fight COVID-19, potentially improving patient outcomes like reducing time in critical care or need for a ventilator. This is its first test against severe COVID-19 infections.

How Is the Trial Designed?

Group I: non-mechanically ventilated, non-critical-care Experimental Treatment 2 Interventions

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

Group II: mechanically ventilated &/or managed in a critical-care Experimental Treatment 2 Interventions

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

N-acetylcysteine is already approved in United States, European Union for the following indications:

Approved in United States as N-acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Approved in European Union as N-acetylcysteine for:

• Paracetamol overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9651994/

N-acetylcysteine for prevention and treatment of COVID-19 Accordingly, preliminary data indicates that NAC improves clinical outcomes in COVID-19 patients [8], [9], and may be considered as part of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024012106

Clinical efficacy of N-acetylcysteine for COVID-19 The results demonstrate that NAC did not improve the outcomes of patients with COVID-19. The following evidence supports this conclusion ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10390689/

N-acetylcysteine reduces severity and mortality in COVID-19 ... This meta-analysis suggests that NAC may have a positive effect on COVID-19 outcomes, specifically, a significant decrease in CRP and D-dimer levels.

4. itjfs.com itjfs.com/index.php/ijfs/article/view/2787

N-acetylcysteine as a promising treatment for COVID-19 NAC-treated patients exhibited significant reduction in C-reactive protein and D-dimer levels, along with higher pO2/FiO2 ratios, minimal stay ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04792021

Effect of N-acetylcysteine on Oxidative Stress in COVID-19 ... Study Overview. The purpose of the study is to assess the potential therapeutic effect of N-acetylcysteine "NAC" in COVID 19 patients. This is a phase 3 trial ...

6. academic.oup.com academic.oup.com/qjmed/article/117/Supplement_1/hcae070.076/7705150

Safety and Efficacy of N-Acetylcysteine as an Adjuvant ... we retrospectively will investigate safety and efficacy of NAC dose given in paracetamol toxicity as an adjuvant therapy in critically ill COVID ...

7. iv.iiarjournals.org iv.iiarjournals.org/content/34/3_suppl/1567

COVID-19: The Potential Role of Copper and N ... - In Vivo Literature data suggests a favourable safety profile for the proposed treatments. In general, RDV was found to be adequately tolerated with typical antiviral ...