Clinical Trial With N-acetylcysteine and Bromhexine for COVID-19

June 28, 2021 updated by: Aldo Ângelo Moreira Lima, Universidade Federal do Ceará

Clinical, Control, Double-blind, Randomized Experimentation With N-acetylcysteine and Bromhexine for COVID-19

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

219

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Ceará
      • Fortaleza, Ceará, Brazil, 60430270
        • Núcleo de Biomedicina - NUBIMED

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Treatment group 1
Control placebo (Vitamin C - 500mg / day, for 10 days)
Drug: Vitamin C
Vitamin C 500 mg / day for ten days
Active Comparator: Treatment group 2
N-acetylcysteine (NAC; 1800 mg / day, for 10 days)
Drug: N-acetylcysteine (NAC)
N-acetylcysteine 1800 mg / day for ten days.
Active Comparator: Treatment group 3
NAC (1800 mg / day) + bromhexine-BMX (32 mg / day for 10 days)
Drug: NAC + Bromhexine (BMX)
NAC + Bromhexine (BMX) 32 mg / day for ten days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.]
Time Frame: Day 7
The categories are as follows: 1 - No signals and symptoms; 2 - One signal or symptom; 3 - Two signals or symptoms; 4 - Three or more signals or symptoms.
Day 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SARS-CoV-2 RNA viral load measurements change. [ Time Frame: Change between Day 1 and Day 7 follow up after enrollment. ]
Time Frame: Day 1 and Day 7
Molecular diagnostic analyzes will be done by Real-Time PCR (qPCR) based on official guidelines determined by the American CDC (CDC-006-00019, Revision: 03; https://www.fda.gov/media/134922/download). The nasopharyngeal swab samples collected (Covid-19 test) will proceed to the nucleic acid isolation (NuAc). All qPCR reactions will be by uniplex diagnosis. Results will be reported in copies of RNA / ml.
Day 1 and Day 7
Proportion of patients with qualitative serum IgM / IgG. [ Time Frame: Proportion of positive patients at Day 7 for IgM / IgG (N; %). ]
Time Frame: Day 7
The IgM / IgG immune response to SARS-CoV-2 will be qualitative measure using rapid diagnostic test provide by Eco Diagnóstica (Nova Lima, MG, Brazil).
Day 7
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. ]
Time Frame: Day 1 and Day 14.
We will use the Luminex XMAP Technology (MAGPIX® System, Merck Co., Kenilworth, NJ) which includes the simultaneous analysis, in the same plasma sample (volume of 25 uL), of a panel of protein markers of pro and anti-inflammatory activity (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). Specific antibodies covalently linked to the carboxylated microspheres containing different specific fluorochromes will be used. Standard curves will be constructed for each protein and then their quantification. Results will be reported in pg / mL.
Day 1 and Day 14.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidade Federal do Ceará

Collaborators

São José Hospital for Infectious Diseases - HSJ
Central Laboratory of Public Health of Ceara - LACEN-CE
Paulista School of Medicine-EPM, UNIFESP
Health Surveillance Secretariat - SVS
Leonardo da Vinci Hospital - HLV
Ceará Health Secretariat - SESA
Municipal Health Secretary - SMS-Fortaleza

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 15, 2021

Primary Completion (Anticipated)

April 9, 2022

Study Completion (Anticipated)

June 9, 2022

Study Registration Dates

First Submitted

June 14, 2021

First Submitted That Met QC Criteria

June 15, 2021

First Posted (Actual)

June 16, 2021

Study Record Updates

Last Update Posted (Actual)

June 30, 2021

Last Update Submitted That Met QC Criteria

June 28, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVANTI-C19

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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