Clinical trial NCT04928495: Clinical Trial With N-acetylcysteine and Bromhexine for COVID-19
Official title: Clinical, Control, Double-blind, Randomized Experimentation With N-acetylcysteine and Bromhexine for COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19
Keywords: N-acetylcysteine
Bromhexine
COVID-19
Clinical trial
Lead sponsor: Universidade Federal do Ceara
Sponsor class: OTHER
Collaborators: name: Paulista School of Medicine-EPM, UNIFESP
name: Health Surveillance Secretariat - SVS
name: Central Laboratory of Public Health of Ceara - LACEN-CE
name: Leonardo da Vinci Hospital - HLV
name: São José Hospital for Infectious Diseases - HSJ
name: Ceará Health Secretariat - SESA
name: Municipal Health Secretary - SMS-Fortaleza
First posted: 2021-06-16
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: (1) Placebo control; (2) N-acetylcysteine treatment (NAC); and (3) NAC + Bromhexine treatment.
Primary purpose: TREATMENT

Brief summary: Clinical, control, double-blind, randomized experimentation with N-acetylcysteine and bromhexine for COVID-19.

Detailed description: Several therapeutic agents have been evaluated for the treatment of COVID-19, but only one, the antiviral drug called remdesivir administered intravenously, has shown to be effective in shortening the duration of the disease by 26.7% in critically ill patients. This proposal has the primary objective (1) to determine the effect of N-acetylcysteine (NAC; reducing substance and complementary viral intercepting action) and combination of NAC + bromhexine (BMX; viral protease inhibitor), on the clinical duration of COVID-19 evaluated on the 7th. day of outpatient follow-up, observing the score of clinical signs and symptoms of the disease. The study has as secondary objectives: (2) to assess the change in viral load by RT-qPCR of SARS-CoV-2 between the 1st, 7th, and 14th. days of the experimental protocol; (3) determine the action of NAC and BMX + NAC on the immune response using the rapid ELISA test (IgM / IgG) to be performed on the 14th. monitoring day of the experimental protocol; and (4) Assess the effect of NAC and BMX + NAC on the change in the serum level of inflammation biomarkers and reducing substances (IL-6, MCP-3, D-dimer, IL1-RA, IL-10, GCSF, TNF- α, MCP-1, IL-2R, MIP-1 alpha, IP-10, IL-8, NT-proBNP, Troponin I, PCR and procalcitonin; glutathione peroxidase-GPx; superoxide dismutase-SOD and catalase-CAT) of patients collected on the 1st. and 14 o. study days. The study will be a prospective, double-blind, placebo control and randomized clinical trial of a total of 219 patients, 73 for each treatment group, with mild to moderate disease, equal to or above 18 years of age, with clinical signs and symptoms. of COVID-19 and certified by the RT-qPCR test for the detection of SARS-CoV-2 viral load. The study will be carried out using the Surveillance, Service and Research Network - REVAP-C19, NUBIMED, FAMED, UFC, Fortaleza, CE in order to facilitate the efficiency of patients' entry into the study. The random groups of treatments will be: (1) Placebo control (Vitamin C - 500 mg / day, for 10 days); (2) N-acetylcysteine (NAC; 1800 mg / day, for 10 days); and (3) NAC (1800 mg / day, for 10 days) + Bromhexine Hydrochloride (BMX; 32 mg / day, for 10 days). The study has the perspective of evaluating the effectiveness of NAC alone or combined with BMX in the duration of the clinical score of mild to moderate cases of COVID-19. The study will also assess secondary parameters such as the effect of drugs on changing viral load, immune response, and changing the inflammatory reaction and reducing substances in the plasma of the study patients. In this sense, the trial plans to minimize the evolution of the disease to severe cases, thus alleviating the collapse of the health system and minimizing the social, economic and health disorders of the pandemic by SARS-CoV-2.

Eligibility criteria: The inclusion criteria will be:

1. patients with clinical signs and symptoms of COVID-19; and
2. patients over 18 years and below 60 years of age.

The exclusion criteria will be:

1. participate in another clinical intervention study;
2. you have a disease or other medical condition that prevents you from using the medications for this intervention;
3. patient incapable of ingesting, retaining and absorbing the intervention medications; and (d) is mentally disabled.

Primary outcomes:
measure: The time to recovery, defined at day 7 days follow up after enrollment, on which a patient met the criteria for category 1 or 2 on the four-category ordinal scale. [Time Frame: Day 7 follow up after enrollment.]
timeFrame: Day 7
Secondary outcomes:
measure: SARS-CoV-2 RNA viral load measurements change. [ Time Frame: Change between Day 1 and Day 7 follow up after enrollment. ]
timeFrame: Day 1 and Day 7
measure: Proportion of patients with qualitative serum IgM / IgG. [ Time Frame: Proportion of positive patients at Day 7 for IgM / IgG (N; %). ]
timeFrame: Day 7
measure: Biomarkers (IL-6, MCP-3, D-dimer, IL1-RA, IL-10, GCSF, TNF-α, MCP-1, IL-2R, MIP-1 alpha, IP-10, IL-8, NT-proBNP, Troponin I, CRP and procalcitonin) measurements change. [ Time Frame: Change between Day 1 and Day 14 follow up after enrollment. ]
timeFrame: Day 1 and Day 14.
Other outcomes:
Locations:
city: Fortaleza
country: Brazil
facility: Núcleo de Biomedicina - NUBIMED
state: Ceará
Study officials:
References: