COVIDPhase 2NCT04374019
Novel Agents for Treatment of High-risk COVID-19 Positive Patients
A Phase 2 study testing Ivermectin, Camostat Mesilate and Artemesia annua in people with COVID and Sars-CoV2, run by Susanne Arnold at 1 site in United States.
Trial summary
This is a multi-arm, phase II trial for rapid efficacy and toxicity assessment of multiple therapies immediately after COVID19 positive testing in high-risk individuals. Therapies include stand-alone or combination treatment with hydroxychloroquine, azithromycin, ivermectin, or camostat mesilate, artemesia annua. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- What is being tested?
- Ivermectin, Camostat Mesilate and Artemesia annua
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2020to 12 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Laboratory-confirmed SARS-CoV-2 infection within the past 7 days or the presence of symptoms or physical examination signs providing high probability of COVID-19 disease
- Patients must have adequate organ and marrow function measured within the last 6 months
- Subjects must have at least one of the following high-risk features for clinical deterioration:
- Hypertension
- Diabetes Mellitus
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- Moderate to severe Chronic Obstructive Pulmonary Disease, Emphysema, Cystic Fibrosis, or Asthma
- Cancer patients who have received any immunosuppressive drugs within a year from enrollment
- Sickle Cell disease or thalessemia
- Age > or = 50
- BMI > or = 30
- Living in a nursing home or long-term facility
- Underlying serious heart condition as determined by the treating physician
- Immunocompromised subject as defined by the treating physician or COVID-19 Telehealth Treatment Team
Who cannot join
- Severe or life threating COVID
- Weight less than 45 kg.
- Pregnant or breast-feeding females
- Subjects on dialysis or with creatinine clearance < 45 ml/min
- Existing DMID Toxicity Scale for Determining Severity of Adverse Events grade 3 or greater hepatic failure
- Previously documented moderate or severe retinopathy or macular degeneration
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- Uncontrolled Seizure disorder
- Prolonged QT, defined as QTc ≥470 milliseconds for men and as QTc ≥480 for women using Bazett's formula
- Known allergy to artesunate, artemisia annua, hydroxychloroquine, macrolides, 4-aminoquinolines, camostat mesilate, or other agents to be used in the trial.
- Currently receiving any study medications for other indications
- Concurrent use of medication that would cause drug-drug interactions
- Patients with psychiatric illness/social situations that would limit compliance
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40532
About this study
Official title: Randomized, Multi-arm Phase II Trial of Novel Agents for Treatment of High-risk COVID-19 Positive Patients
This is a multi-arm, phase II trial for rapid efficacy and toxicity assessment of multiple therapies immediately after COVID19 positive testing in high-risk individuals. Therapies include stand-alone or combination treatment with hydroxychloroquine, azithromycin, ivermectin, or camostat mesilate, artemesia annua. The hypothesis of this study is that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus replication in will be devoid of additional moderate to severe toxicities, will prevent clinical deterioration, and will improve viral clearance in high risk individuals.
Read the detailed description
Coronavirus Disease 2019 (COVID-19) is a highly contagious disease, caused by a novel enveloped RNA beta-coronavirus, also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The first case of this unprecedented outbreak "pneumonia of unknown etiology" was reported in Wuhan City, Hubei Province, China on December 8th, 2019 and reported to the World Health Organization (WHO) on December 31st, 2019. WHO declared a COVID-19 global emergency on January 30, 2020, and then categorized the outbreak as a pandemic on March 11, 2020. As of April 22, 2020, more than 2,628,894 confirmed cases of COVID-19 worldwide and 182,740 people globally have died from COVID-19 since it emerged in China, according to the data from Johns Hopkins University.
While the majority of patients with COVID-19 develop mild or uncomplicated illness, approximately 20-30% of hospitalized patients have required intensive care support and 5% of those have multi-organ failure or shock. The case fatality rate ranges from 1 to 4% and it is higher among those with pre-existing comorbid conditions such as cardiovascular disease, diabetes mellitus, obesity, chronic respiratory disease, hypertension and cancer. The vast majority of patients present with fever (83-99%), cough (59-82%), fatigue (44-70%), anorexia (40-84%), shortness of breath (31-40%), sputum production (28-33%), myalgias (11-35%). Less than 10% of patients will present with headache, confusion, rhinorrhea, sore throat, hemoptysis, vomiting, or diarrhea. Anosmia or ageusia proceeding the onset of respiratory symptoms has been anecdotally reported.
To date, treatments for COVID-19 in high risks individuals remain experimental and therapeutic strategies to deal with the infection are at best supportive, with prevention aimed at reducing transmission in the community as the best weapon. No proven therapies have been demonstrated to prevent the progression of COVID-19 to severe illness and this is a critical unmet need for high-risk individuals and warrants study. Recently, the Infectious Disease Society of America has made recommendations for the treatment of patients with COVID-19, focusing on inpatient care, and recommending randomized trials where possible as the best step to improve treatment outcomes and to increase our understanding of this coronavirus pandemic. Discoveries in this area may inform clinicians on effective treatment for low-risk individuals who progress to severe illness, as well.
- Being tested
- Ivermectin, Camostat Mesilate, Artemesia annua, Artesunate
- Keywords
- high-risk
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvermectinDrug
Ivermectin:
Days 1-2: Weight < 75kg: 4 tabs (12 mg total daily dose) Days 1-2: Weight > 75kg: 5 tabs (15 mg total daily dose)
Camostat MesilateDrug
Days 1-14: 2 tab TID after a meal (600 mg total daily dose)
Artemesia annuaDietary supplement
Days 1-14: tea or coffee pod TID (1350 mg total daily dose)
ArtesunateDrug
Days 1-14:
| Study group | Role | What they receive |
|---|---|---|
| Arm C: Ivermectin | Experimental | Ivermectin Receives: Drug: Ivermectin |
| Arm D: Camostat Mesilate | Experimental | Camostat Mesilate Receives: Drug: Camostat Mesilate |
| Arm E: Artemesia annua | Experimental | Artemesia annua tea or coffee Receives: Dietary Supplement: Artemesia annua |
| Arm F: Artesunate | Experimental | Artesunate Receives: Drug: Artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Deterioration
Number of patients experiencing clinical deterioration. Clinical deterioration is defined as a less than a 2-point change from the initial COVID 7-Point Ordinal Outcomes Scale within 14 days from the study start. This scale ranges from 1-7. Lower scores indicate worse outcomes (death); higher scores indicate fewer symptoms and better outcomes.
Measured: 14 days
Secondary outcomes (12)
Change in Viral Load
The change in (clearance of) viral RNA will be measured by PCR testing at days 1, 14, 28, and 40 days.
Measured: 40 days
Rate of Organ Failure
Number of patients that experienced severe respiratory or other organ failure.
Measured: 28 days
Progression to ICU Care or Ventilation
Percentage of patients requiring ICU admission or ventilation.
Measured: 28 days
Number of Participants Who Had a Change in Clinical Status Measured by Decrease in COVID 7-point Ordinal Scale
Number of participants who died or had greater than a 2-point decrease in COVID 7-Point Ordinal Outcomes Scale from Day to Day 14.
COVID 7-point ordinal outcomes scale:
- Death
- Hospitalized on invasive mechanical ventilation or ECMO
- Hospitalized on non-invasive ventilation or high flow nasal cannula
- Hospitalized on supplemental oxygen
- Hospitalized not on supplemental oxygen
- Not hospitalized with limitation in activity (continued symptoms)
- Not hospitalized without limitation in activity (no symptoms)
Measured: 14 days
Mortality
Percentage of patients who have died by day 14.
Measured: 14 days
Rate of Severe Adverse Events
Percentage of patients experiencing severe adverse events, defined as grade 3 non-hematologic or greater by DMID Toxicity Scale for Determining Severity of Adverse Events.
Measured: 14 days
Number of Patients That Required Oxygen Supplementation
Number of patients that required oxygen supplementation during study treatment Days 1-28
Measured: 28 days
Number of Patients That Required Mechanical Ventilation
Number of patients that required mechanical ventilation during the study period. Days 1-28
Measured: 28 days
Number of Patients Who Required Vasopressors
Number of patients who required vasopressor treatment Days 1 to 28
Measured: 28 days
Number of Patients Who Required ICU Services
Number of patients who required ICU services during study treatment Days 1-28.
Measured: 28 days
Number of Patients That Required Hospitalization
Number of patients that required hospitalization during study treatment
Measured: 28 days
Heart Function
Proportion of patients with significant changes in ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes, or abnormalities including severe QTc prolongation of > 500 ms.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2020
- Study start1 May 2020
- Primary completion21 Dec 2020
- Study completion12 Jan 2022
Why it stopped: slow accrual,
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVIDStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Susanne Arnold
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Susanne Arnold, University of Kentucky
- Investigators
- Susanne Arnold, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04374019
- Sponsor's protocol ID
- MCC-20-COVID-01-PMC
- Status last verified
- Jan 2022
- First submitted
- 1 May 2020
- Last updated
- 20 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Multi-arm Phase II Trial of Novel Agents for Treatment of High-risk COVID-19 Positive Patients
- ClinicalTrials.gov ID
- NCT04374019
- Acronym / sponsor ID
- MCC-20-COVID-01-PMC
- Keywords
- high-risk
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual,
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Susanne ArnoldUniversity, hospital or other
- Study start
- 1 May 2020 (actual)
- Primary completion
- 21 Dec 2020 (actual)
- Study completion
- 12 Jan 2022 (actual)
- First posted
- 5 May 2020 (actual)
- Results
- Posted 20 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-arm, phase II trial for rapid efficacy and toxicity assessment of multiple therapies immediately after COVID19 positive testing in high-risk individuals. Therapies include stand-alone or combination treatment with hydroxychloroquine, azithromycin, ivermectin, or camostat mesilate, artemesia annua. The hypothesis of this study is that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus replication in will be devoid of additional moderate to severe toxicities, will prevent clinical deterioration, and will improve viral clearance in high risk individuals.
Detailed description
Coronavirus Disease 2019 (COVID-19) is a highly contagious disease, caused by a novel enveloped RNA beta-coronavirus, also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The first case of this unprecedented outbreak "pneumonia of unknown etiology" was reported in Wuhan City, Hubei Province, China on December 8th, 2019 and reported to the World Health Organization (WHO) on December 31st, 2019. WHO declared a COVID-19 global emergency on January 30, 2020, and then categorized the outbreak as a pandemic on March 11, 2020. As of April 22, 2020, more than 2,628,894 confirmed cases of COVID-19 worldwide and 182,740 people globally have died from COVID-19 since it emerged in China, according to the data from Johns Hopkins University.
While the majority of patients with COVID-19 develop mild or uncomplicated illness, approximately 20-30% of hospitalized patients have required intensive care support and 5% of those have multi-organ failure or shock. The case fatality rate ranges from 1 to 4% and it is higher among those with pre-existing comorbid conditions such as cardiovascular disease, diabetes mellitus, obesity, chronic respiratory disease, hypertension and cancer. The vast majority of patients present with fever (83-99%), cough (59-82%), fatigue (44-70%), anorexia (40-84%), shortness of breath (31-40%), sputum production (28-33%), myalgias (11-35%). Less than 10% of patients will present with headache, confusion, rhinorrhea, sore throat, hemoptysis, vomiting, or diarrhea. Anosmia or ageusia proceeding the onset of respiratory symptoms has been anecdotally reported.
To date, treatments for COVID-19 in high risks individuals remain experimental and therapeutic strategies to deal with the infection are at best supportive, with prevention aimed at reducing transmission in the community as the best weapon. No proven therapies have been demonstrated to prevent the progression of COVID-19 to severe illness and this is a critical unmet need for high-risk individuals and warrants study. Recently, the Infectious Disease Society of America has made recommendations for the treatment of patients with COVID-19, focusing on inpatient care, and recommending randomized trials where possible as the best step to improve treatment outcomes and to increase our understanding of this coronavirus pandemic. Discoveries in this area may inform clinicians on effective treatment for low-risk individuals who progress to severe illness, as well.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm C: Ivermectin | Experimental | Drug: IvermectinIvermectin |
| Arm D: Camostat Mesilate | Experimental | Drug: Camostat MesilateCamostat Mesilate |
| Arm E: Artemesia annua | Experimental | Dietary Supplement: Artemesia annuaArtemesia annua tea or coffee |
| Arm F: Artesunate | Experimental | Drug: ArtesunateArtesunate |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age ≥18 years
- Laboratory-confirmed SARS-CoV-2 infection within the past 7 days or the presence of symptoms or physical examination signs providing high probability of COVID-19 disease
- Patients must have adequate organ and marrow function measured within the last 6 months
- Subjects must have at least one of the following high-risk features for clinical deterioration:
Key exclusion criteria (12 listed)
- Severe or life threating COVID
- Weight less than 45 kg.
- Pregnant or breast-feeding females
- Subjects on dialysis or with creatinine clearance < 45 ml/min
- Existing DMID Toxicity Scale for Determining Severity of Adverse Events grade 3 or greater hepatic failure
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 |
|---|---|---|
| IvermectinIvermectin: Days 1-2: Weight < 75kg: 4 tabs (12 mg total daily dose) Days 1-2: Weight > 75kg: 5 tabs (15 mg total daily dose) | Drug | Arm C: Ivermectin |
| Camostat MesilateDays 1-14: 2 tab TID after a meal (600 mg total daily dose) | Drug | Arm D: Camostat Mesilate |
| Artemesia annuaDays 1-14: tea or coffee pod TID (1350 mg total daily dose) | Dietary supplement | Arm E: Artemesia annua |
| ArtesunateDays 1-14: | Drug | Arm F: Artesunate |
Primary outcome
Clinical Deterioration
Time frame: 14 days
Number of patients experiencing clinical deterioration. Clinical deterioration is defined as a less than a 2-point change from the initial COVID 7-Point Ordinal Outcomes Scale within 14 days from the study start. This scale ranges from 1-7. Lower scores indicate worse outcomes (death); higher scores indicate fewer symptoms and better outcomes.
12 secondary outcomes
Change in Viral Load
Time frame: 40 days
Rate of Organ Failure
Time frame: 28 days
Progression to ICU Care or Ventilation
Time frame: 28 days
Number of Participants Who Had a Change in Clinical Status Measured by Decrease in COVID 7-point Ordinal Scale
Time frame: 14 days
Mortality
Time frame: 14 days
Rate of Severe Adverse Events
Time frame: 14 days
Number of Patients That Required Oxygen Supplementation
Time frame: 28 days
Number of Patients That Required Mechanical Ventilation
Time frame: 28 days
Number of Patients Who Required Vasopressors
Time frame: 28 days
Number of Patients Who Required ICU Services
Time frame: 28 days
Number of Patients That Required Hospitalization
Time frame: 28 days
Heart Function
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Susanne Arnold, MD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivermectin, Camostat Mesilate and Artemesia annua in people with COVID and Sars-CoV2, run by Susanne Arnold at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 12 exclusion criteria. 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: stopped early, as of the sponsor's last update on 20 Jan 2022. 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 United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical Deterioration (time frame: 14 days). 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 20 Jan 2022.