COVID-19Phase 3NCT04928495
Clinical Trial With N-acetylcysteine and Bromhexine for COVID-19
A Phase 3 study testing Vitamin C, N-acetylcysteine (NAC) and NAC + Bromhexine (BMX) in people with COVID-19, run by Universidade Federal do Ceara at 1 site in Brazil.
Trial summary
Clinical, control, double-blind, randomized experimentation with N-acetylcysteine and bromhexine for COVID-19. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Vitamin C, N-acetylcysteine (NAC) and NAC + Bromhexine (BMX)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 219 participants
- Where
- 1 siteBrazil
- Study dates
- 15 Jul 2021to 9 Jun 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
The inclusion criteria will be:
- patients with clinical signs and symptoms of COVID-19; and
- patients over 18 years and below 60 years of age.
The exclusion criteria will be:
- participate in another clinical intervention study;
- you have a disease or other medical condition that prevents you from using the medications for this intervention;
- patient incapable of ingesting, retaining and absorbing the intervention medications; and (d) is mentally disabled.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin CDrug
Vitamin C 500 mg / day for ten days
N-acetylcysteine (NAC)Drug
N-acetylcysteine 1800 mg / day for ten days.
NAC + Bromhexine (BMX)Drug
NAC + Bromhexine (BMX) 32 mg / day for ten days.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group 1 | Placebo comparator | Control placebo (Vitamin C - 500mg / day, for 10 days) Receives: Drug: Vitamin C |
| Treatment group 2 | Active comparator | N-acetylcysteine (NAC; 1800 mg / day, for 10 days) Receives: Drug: N-acetylcysteine (NAC) |
| Treatment group 3 | Active comparator | NAC (1800 mg / day) + bromhexine-BMX (32 mg / day for 10 days) Receives: Drug: NAC + Bromhexine (BMX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.]
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.
Measured: Day 7
Secondary outcomes (3)
SARS-CoV-2 RNA viral load measurements change. [ Time Frame: Change between Day 1 and Day 7 follow up after enrollment. ]
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.
Measured: 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; %). ]
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).
Measured: 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. ]
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.
Measured: Day 1 and Day 14.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2021
- Study start15 Jul 2021 (estimated)
- Primary completion9 Apr 2022 (estimated)
- Study completion9 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- (1) Placebo control; (2) N-acetylcysteine treatment (NAC); and (3) NAC + Bromhexine treatment.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 219 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidade Federal do Ceara
- Sponsor type
- University, hospital or other
- Collaborators
- Paulista School of Medicine-EPM, UNIFESP, Health Surveillance Secretariat - SVS, Central Laboratory of Public Health of Ceara - LACEN-CE, Leonardo da Vinci Hospital - HLV, São José Hospital for Infectious Diseases - HSJ, Ceará Health Secretariat - SESA, Municipal Health Secretary - SMS-Fortaleza
- Responsible party
- Principal investigator, Aldo Ângelo Moreira Lima, Universidade Federal do Ceara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04928495
- Sponsor's protocol ID
- AVANTI-C19
- Status last verified
- Jun 2021
- First submitted
- 14 Jun 2021
- Last updated
- 30 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical, Control, Double-blind, Randomized Experimentation With N-acetylcysteine and Bromhexine for COVID-19
- ClinicalTrials.gov ID
- NCT04928495
- Acronym / sponsor ID
- AVANTI-C19
- Conditions
- COVID-19
- Keywords
- N-acetylcysteine, Bromhexine, COVID-19, Clinical trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 219 participants (estimated)
- Lead sponsor
- Universidade Federal do CearaUniversity, hospital or other
- Collaborators
- Paulista School of Medicine-EPM, UNIFESP, Health Surveillance Secretariat - SVS, Central Laboratory of Public Health of Ceara - LACEN-CE, Leonardo da Vinci Hospital - HLV, São José Hospital for Infectious Diseases - HSJ, Ceará Health Secretariat - SESA, Municipal Health Secretary - SMS-Fortaleza
- Study start
- 15 Jul 2021 (estimated)
- Primary completion
- 9 Apr 2022 (estimated)
- Study completion
- 9 Jun 2022 (estimated)
- First posted
- 16 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- (1) Placebo control; (2) N-acetylcysteine treatment (NAC); and (3) NAC + Bromhexine treatment.
| Arm | Type | Receives |
|---|---|---|
| Treatment group 1 | Placebo comparator | Drug: Vitamin CControl placebo (Vitamin C - 500mg / day, for 10 days) |
| Treatment group 2 | Active comparator | Drug: N-acetylcysteine (NAC)N-acetylcysteine (NAC; 1800 mg / day, for 10 days) |
| Treatment group 3 | Active comparator | Drug: NAC + Bromhexine (BMX)NAC (1800 mg / day) + bromhexine-BMX (32 mg / day for 10 days) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin CVitamin C 500 mg / day for ten days | Drug | Treatment group 1 |
| N-acetylcysteine (NAC)N-acetylcysteine 1800 mg / day for ten days. | Drug | Treatment group 2 |
| NAC + Bromhexine (BMX)NAC + Bromhexine (BMX) 32 mg / day for ten days. | Drug | Treatment group 3 |
Primary outcome
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.
3 secondary outcomes
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
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
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin C, N-acetylcysteine (NAC) and NAC + Bromhexine (BMX) in people with COVID-19, run by Universidade Federal do Ceara at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.] (time frame: Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2021.