Novel Agents for Treatment of High-risk COVID-19 Positive Patients
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|ClinicalTrials.gov Identifier: NCT04374019|
Recruitment Status : Recruiting
First Posted : May 5, 2020
Last Update Posted : November 6, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID Sars-CoV2||Drug: Ivermectin Drug: Camostat Mesilate Dietary Supplement: Artemesia annua Drug: Artesunate||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||240 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized, Multi-arm Phase II Trial of Novel Agents for Treatment of High-risk COVID-19 Positive Patients|
|Actual Study Start Date :||May 1, 2020|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||May 2021|
Experimental: Arm C: 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)
Experimental: Arm D: Camostat Mesilate
Drug: Camostat Mesilate
Days 1-14: 2 tab TID after a meal (600 mg total daily dose)
Experimental: Arm E: Artemesia annua
Artemesia annua tea or coffee
Dietary Supplement: Artemesia annua
Days 1-14: tea or coffee pod TID (1350 mg total daily dose)
Experimental: Arm F: Artesunate
- Clinical Deterioration [ Time Frame: 14 days ]Proportion 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.
- Change in Viral Load [ Time Frame: 40 days ]The change in (clearance of) viral RNA will be measured by PCR testing at days 1, 14, 28, and 40 days.
- Rate of Organ Failure [ Time Frame: 28 days ]Percentage of patients that experience severe respiratory or other organ failure.
- Progression to ICU Care or Ventilation [ Time Frame: 28 days ]Percentage of patients requiring ICU admission or ventilation.
- Change in Clinical Status [ Time Frame: 14 days ]Clinical status will be assessed using the COVID 7-Point Ordinal Outcomes Scale. This scale ranges from 1-7. Lower scores indicate worse outcomes; higher scores indicate fewer symptoms and better outcomes.
- Mortality [ Time Frame: 14 days ]Percentage of patients who have died by day 14.
- Rate of severe adverse events [ Time Frame: 14 days ]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.
- Oxygen-free days [ Time Frame: 28 days ]Number of days patients do not require oxygen supplementation.
- Ventilator-free days [ Time Frame: 28 days ]Number of days patients do not require mechanical ventilation.
- Vasopressor-free days [ Time Frame: 28 days ]Number of days patients do not require vasopressor treatment.
- ICU-free days [ Time Frame: 28 days ]Number of days patients do not require ICU services.
- Hospital-free days [ Time Frame: 28 days ]Number of days patients do not require hospitalization.
- Patients meeting Hy's Law criteria [ Time Frame: 28 days ]Proportion of patients meeting Hy's law criteria.
- Liver Function [ Time Frame: 28 days ]
Proportion of patients with changes in the following liver function tests:
- Any ALT or AST ≥ 5 x ULN;
- any AST or ALT ≥ 3 x ULN together with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (eosinophil percent or count above the ULN);
- Persistent ALT ≥ 3 x ULN for a period of more than 4 weeks
- Heart Function [ Time Frame: 28 days ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04374019
|United States, Kentucky|
|University of Kentucky Markey Cancer Center||Recruiting|
|Lexington, Kentucky, United States, 40532|
|Contact: Susanne Arnold, M.D. 859-323-8043 email@example.com|
|Principal Investigator: Susanne Arnold, M.D.|
|Principal Investigator:||Susanne Arnold, MD||University of Kentucky|