Efficacy of N-acetyl Cysteine in Severe COVID-19 Patients: A Randomized Controlled Phase III Clinical Trial
Arash Rahimi, Hamidreza Samimagham, Ladan Hajiabdolrrasouli, Mehdi Hassani Azad, Ali Salimi Asl, Fatemeh Khajavi Mayvan, Elham Boushehri, Mohsen Arabi, Sepideh Pazhoohesh, Mitra Kazemi Jahromi
Jundishapur Journal of Natural Pharmaceutical Products, doi:10.5812/jjnpp-129817
Background: Today, various drugs have been investigated as the primary or complementary treatment for coronavirus disease 2019 . N-acetylcysteine (NAC) has been used as a mucolytic in pulmonary diseases. This drug apparently contributes to the retrieval of the intracellular antioxidant system. Objectives: This study aimed to determine the efficacy of NAC in severe COVID-19 patients admitted to the intensive care unit (ICU). Methods: This single-blinded randomized controlled phase III clinical trial included 40 patients with confirmed COVID-19 (based on polymerase chain reaction) admitted to the Shahid Mohammadi Hospital's ICU, Bandar Abbas, Iran, in 2020. All cases had severe COVID-19. They were allocated randomly to two equal groups. Patients in the control group received standard drug therapy based on the treatment protocol of the national COVID-19 committee, while those in the NAC group received a single dose of intravenous NAC (300 mg/kg) upon admission to the ICU in addition to standard drug treatment. Clinical status and laboratory tests were done on admission to the ICU and then 14 days later or at discharge without knowing the patient grouping. Results: The two groups were comparable regarding age, gender, and other baseline laboratory and clinical parameters. At the final evaluation, respiratory rate (21.25 ± 4.67 vs. 27.37 ± 6.99 /min) and D-dimer (186.37 ± 410.23 vs. 1339.04 ± 2183.87 ng/mL) were significantly lower in the NAC group (P = 0.004 and P = 0.030, respectively). Also, a lower percentage of patients in the NAC group had lactate dehydrogenase (LDH) ≤ 245 U/L (0% vs. 25%, P = 0.047). Although the length of ward and ICU stay was shorter in the NAC group than in controls, the difference was statistically insignificant (P = 0.598 and P = 0.629, respectively). Mortality, on the other hand, was 75% in the control group and 50% in the NAC group, with no statistically significant difference (P = 0.102). Concerning the change in the study parameters, only the decrease in diastolic blood pressure (DBP) was significantly higher with NAC (P = 0.042). The intubation and mechanical ventilation rates were higher, while oxygen with mask and nasal oxygen rates were lower with NAC, but the difference was statistically insignificant. Conclusions: Based on the current research, NAC is related to a significant decrease in RR, D-dimer, and DBP in severe COVID-19. Also, LDH was significantly lower in the NAC group than in the controls. More research with larger sample sizes is needed to validate the current study results.
Authors' Contribution: A. R and M. K. J. contributed to the conception and design. Other authors contributed to data collection and manuscript drafting. M. K. J. supervised the study. All authors approved the final version of the manuscript.
Clinical Trial Registration Code: This study is registered in the IRCT with the code IRCT20200509047364N3 (link: www.irct.ir/trial/54372 ).
Conflict of Interests: The authors have no conflict of interests.
Data Reproducibility: The dataset presented in the study is available on request from the corresponding author during submission or after its publication. The data are not publicly available since this is one of the new attempts to treat ICU-admitted COVID-19 patients. Ethical Approval: This study is approved under the ethical approval code of IR.HUMS.REC.1399.539 (link: ethics.research.ac.ir/form/n12u8iqoje51gyss.pdf). Funding/Support: No funding/support was received.
Informed Consent: Written informed consent was signed by all participants.
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doi:10.1186/s13054-020-03015-0DOI record:
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"abstract": "<jats:p>Background: Today, various drugs have been investigated as the primary or complementary treatment for coronavirus disease 2019 (COVID-19). N-acetylcysteine (NAC) has been used as a mucolytic in pulmonary diseases. This drug apparently contributes to the retrieval of the intracellular antioxidant system. Objectives: This study aimed to determine the efficacy of NAC in severe COVID-19 patients admitted to the intensive care unit (ICU). Methods: This single-blinded randomized controlled phase III clinical trial included 40 patients with confirmed COVID-19 (based on polymerase chain reaction) admitted to the Shahid Mohammadi Hospital’s ICU, Bandar Abbas, Iran, in 2020. All cases had severe COVID-19. They were allocated randomly to two equal groups. Patients in the control group received standard drug therapy based on the treatment protocol of the national COVID-19 committee, while those in the NAC group received a single dose of intravenous NAC (300 mg/kg) upon admission to the ICU in addition to standard drug treatment. Clinical status and laboratory tests were done on admission to the ICU and then 14 days later or at discharge without knowing the patient grouping. Results: The two groups were comparable regarding age, gender, and other baseline laboratory and clinical parameters. At the final evaluation, respiratory rate (21.25 ± 4.67 vs. 27.37 ± 6.99 /min) and D-dimer (186.37 ± 410.23 vs. 1339.04 ± 2183.87 ng/mL) were significantly lower in the NAC group (P = 0.004 and P = 0.030, respectively). Also, a lower percentage of patients in the NAC group had lactate dehydrogenase (LDH) ≤ 245 U/L (0% vs. 25%, P = 0.047). Although the length of ward and ICU stay was shorter in the NAC group than in controls, the difference was statistically insignificant (P = 0.598 and P = 0.629, respectively). Mortality, on the other hand, was 75% in the control group and 50% in the NAC group, with no statistically significant difference (P = 0.102). Concerning the change in the study parameters, only the decrease in diastolic blood pressure (DBP) was significantly higher with NAC (P = 0.042). The intubation and mechanical ventilation rates were higher, while oxygen with mask and nasal oxygen rates were lower with NAC, but the difference was statistically insignificant. Conclusions: Based on the current research, NAC is related to a significant decrease in RR, D-dimer, and DBP in severe COVID-19. Also, LDH was significantly lower in the NAC group than in the controls. More research with larger sample sizes is needed to validate the current study results.</jats:p>",
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