Trial of Hydroxychloroquine In Covid-19 Kinetics

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Phase 2/3 Trial of Hydroxychloroquine In Covid-19 Kinetics

Conditions
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Covid 19, Corona Virus Infection

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo verses medication clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br>Subjects in this arm will receive the study drug | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 800 mg initial dose then 6-8 hours later HCQ 600 mg, then 200 mg three times per day for 4 days.<br>* Other names: plaquenil;|
| Placebo Comparator: Placebo<br>Subjects in this arm will take placebo for 6 days | Other: Placebo<br>* Placebo take 4 tabs, then 6-8 hours later take 3 tabs, then take 1 tab three times per day for 4 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Are Virus Free | Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs | 7 days after initiation of trial | 
| 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) . | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Are Hospitalized for Covid 19 Infection | Number of subjects in each arm who are hospitalized for Covid 19 infection | 14 days | 
| Number of Participants Who Die Secondary to Covid 19 Infection | Number of subjects in each arm who die secondary to Covid-19 infection | 70 Days (10 weeks) | 
| Number of Participants Who Have Confirmed Covid 19 Infection | Number of subjects in each arm who have confirmed Covid-19 infection | 14 days | 
| 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 | 14 days | 
| Immunity to Covid-19 | Blood tests to determine level of immunity in each subject | 70 days (10 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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covid 19, plaquenil, hydroxychloroquine