Corona Virus Infection, Covid 19
Conditions
Keywords
covid 19, plaquenil, hydroxychloroquine
Brief summary
To test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.
Detailed description
Hydroxychloroquine (HCQ), which is a less toxic derivative of chloroquine (CQ), has been shown to be effective in inhibiting Covid-19 infection in vitro. The evidence from clinical research trials is sparse and has many flaws. Much of the Chinese experience with Chloroquine comes from a letter to the editor and a news briefing/conference held on February 15, 2020. The letter describes experience with more than 100 patients treated with CQ in multicenter clinical trials but the letter provides no quantitative data to back their claims. At least one non-randomized clinical trial has been performed in Europe. Covid-19 infected patients received 10 days of HCQ daily and underwent daily testing of viral loads from nasopharyngeal swabs. The subjects receiving HCQ were much more likely (P\<0.02) to clear their viral load than subjects who did not receive HCQ. The study had many flaws, which make the conclusions less valuable than rigorously designed randomized clinical trial. This study is designed as a randomized, blinded trial to either confirm or refute the efficacy of HCQ in early treatment of Covid19 infection to ameliorate disease severity, and reduce viral load.
Interventions
DRUGHydroxychloroquine
Hydroxychloroquine 800 mg initial dose then 6-8 hours later HCQ 600 mg, then 200 mg three times per day for 4 days.
OTHERPlacebo
Placebo take 4 tabs, then 6-8 hours later take 3 tabs, then take 1 tab three times per day for 4 days.
Sponsors
University of South Alabama
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Blinded to subject and investigators
Intervention model description
Randomized placebo verses medication clinical trial
Eligibility
Sex/Gender
ALL
Age
19 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Symptoms occurring within 3 days prior to patient presenting to USA Facility for PCR nasopharyngeal swab * Nasopharyngeal swab positive for Covid-19 infection and/or exposure and/or symptoms congruent with fever and cough * Male or Female age 19 to 89 years * Able to take oral medications * Patients not requiring hospitalization * Provision of informed consent
Exclusion criteria
* Known history of EKG QTc prolongation abnormality * Contraindication or allergy to hydroxychloroquine * Retinal eye disease * Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency * Known chronic kidney disease, stage 4 or 5 or receiving dialysis * Weight \< 40 kg * Current use of: hydroxychloroquine or cardiac medicines of: flecainide, Tambocor; amiodarone, Cordarone, Pacerone; digoxin or Digox, Digitek, Lanoxin; procainamide or Procan, Procanbid, propafenone, Rythmal) * Known hepatic disease (cirrhosis, hepatitis) * Active treatment for cancer (chemotherapy, radiation, surgery within 3 months * On immunosuppressive drugs steroids, antirejection medications. * Recipient of solid organ transplant * Pregnancy/breastfeeding * Past medical history Porphyria (may exacerbate disease) * PMH Psoariasis (can worsen disease) * No access to internet or email * Current suicidal thoughts according to Columbia scale * In the screening process before signing consent, subjects will be asked if they are suicidal. If this response is yes, patients will be excluded from trial and directed to the National Suicide Prevention Lifeline: 1-800-273-8255.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Are Virus Free | 7 days after initiation of trial | Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs |
| Disease Severity | 6 days | Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Have Confirmed Covid 19 Infection | 14 days | Number of subjects in each arm who have confirmed Covid-19 infection |
| Number of Participants Who Are Hospitalized for Covid 19 Infection | 14 days | Number of subjects in each arm who are hospitalized for Covid 19 infection |
| Immunity to Covid-19 | 70 days (10 weeks) | Blood tests to determine level of immunity in each subject |
| Number of Participants Who Discontinue or Withdraw Medication Use for Any Reason | 14 days | Number of subjects in each arm who discontinue or withdraw medication use for any reason |
| Number of Participants Who Die Secondary to Covid 19 Infection | 70 Days (10 weeks) | Number of subjects in each arm who die secondary to Covid-19 infection |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Subjects in this arm will receive the study drug
Hydroxychloroquine: Hydroxychloroquine 800 mg initial dose then 6-8 hours later HCQ 600 mg, then 200 mg three times per day for 4 days. | 1 |
| Control Subjects in this arm will take placebo for 6 days
Placebo: Placebo take 4 tabs, then 6-8 hours later take 3 tabs, then take 1 tab three times per day for 4 days. | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Treatment | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
Disease Severity
Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .
Time frame: 6 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Disease Severity | no COVID19 illness (score of 1) | 1 Participants |
| Treatment | Disease Severity | COVID19 illness with hospitalization (score of 3) | 0 Participants |
| Treatment | Disease Severity | COVID19 illness with no hospitalization (score of 2) | 0 Participants |
| Treatment | Disease Severity | Covid 19 with death (Score of 5) | 0 Participants |
| Treatment | Disease Severity | Covid 19 with care requiring hospitalization (score of 4) | 0 Participants |
| Control | Disease Severity | Covid 19 with death (Score of 5) | 0 Participants |
| Control | Disease Severity | Covid 19 with care requiring hospitalization (score of 4) | 0 Participants |
| Control | Disease Severity | no COVID19 illness (score of 1) | 0 Participants |
| Control | Disease Severity | COVID19 illness with no hospitalization (score of 2) | 1 Participants |
| Control | Disease Severity | COVID19 illness with hospitalization (score of 3) | 0 Participants |
Primary
Number of Participants Who Are Virus Free
Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs
Time frame: 7 days after initiation of trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Number of Participants Who Are Virus Free | 0 participants |
| Control | Number of Participants Who Are Virus Free | 0 participants |
Secondary
Immunity to Covid-19
Blood tests to determine level of immunity in each subject
Time frame: 70 days (10 weeks)
Population: Participants refused blood draw. Data was not collected
Secondary
Number of Participants Who Are Hospitalized for Covid 19 Infection
Number of subjects in each arm who are hospitalized for Covid 19 infection
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Number of Participants Who Are Hospitalized for Covid 19 Infection | 0 Participants |
| Control | Number of Participants Who Are Hospitalized for Covid 19 Infection | 0 Participants |
Secondary
Number of Participants Who Die Secondary to Covid 19 Infection
Number of subjects in each arm who die secondary to Covid-19 infection
Time frame: 70 Days (10 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Number of Participants Who Die Secondary to Covid 19 Infection | 0 Participants |
| Control | Number of Participants Who Die Secondary to Covid 19 Infection | 0 Participants |
Secondary
Number of Participants Who Discontinue or Withdraw Medication Use for Any Reason
Number of subjects in each arm who discontinue or withdraw medication use for any reason
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Number of Participants Who Discontinue or Withdraw Medication Use for Any Reason | 0 Participants |
| Control | Number of Participants Who Discontinue or Withdraw Medication Use for Any Reason | 1 Participants |
Secondary
Number of Participants Who Have Confirmed Covid 19 Infection
Number of subjects in each arm who have confirmed Covid-19 infection
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Number of Participants Who Have Confirmed Covid 19 Infection | 1 Participants |
| Control | Number of Participants Who Have Confirmed Covid 19 Infection | 2 Participants |