Rapid Development and Implementation of a Remote ECG-monitored Prospective Randomized Clinical Trial During a Pandemic: Hydroxychloroquine Prophylaxis in COVID-19 Household Contacts

Study Overview
=================
Brief Summary
-----------------
organizing an entirely no in-person contact clinical trial is feasible during a 22 COVID-19 pandemic 23 Remote smartphone 6-lead ECG monitoring is possible even in a group unfamiliar 24 with the technology 25 Hydroxychloroquine used prophylactically at 200 mg BID had no observable 26 cardiotoxicity 27 Additional study using this technique is warranted to look at reliability and cost-28 effectiveness

Detailed Description
-----------------
Household members were contacted by telephone and provided consent forms via E-mail electronic signatures. Randomization was 2:1 to HCQ 200 mg BID or observation for 10 days with total follow-up of 14 days. COVID status was determined by home saliva PCR assay on days 1 and 14. Study drug was shipped to participants. Data of daily symptoms and 6-lead ECGs using a smartphone KardiaMobile® 6L application were collected.

Official Title
-----------------
Rapid Development and Implementation of a Remote ECG-monitored Prospective Randomized Clinical Trial During a Pandemic: Hydroxychloroquine Prophylaxis in COVID-19 Household Contacts

Conditions
-----------------
Covid19, Hydroxychloroquine, Coronavirus Infection, Transmission, Prophylaxis

Intervention / Treatment
-----------------
* Drug: Hydroxychloroquine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: exposure to a COVID-19-infected individual in the same household within five days of diagnosis; age >18 years; ability to give informed consent to participate in a clinical study; ability to swallow oral medications; access to a smartphone Exclusion Criteria: allergy or intolerance to hydroxychloroquine (PlaquenilR); weight less than 85 pounds; eye disease affecting the retina; severe kidney or liver disease; G6PD-deficiency; porphyria; long QTc EKG abnormality or family history of this; other major EKG abnormalities; taking medications that can affect the QT interval including flecainide, amiodarone, digoxin, procainamide, propafenone, sotalol, quinidine, dofetilide, levofloxacin, ciprofloxacin, azithromycin, erythromycin, amitriptyline, doxepin, desipramine, imipramine, fluoxetine, sertraline, venlafaxine, quetiapine, haloperidol, droperidol, thioridazine, ziprasidone, furosemide, sumatriptan or zolmitriptan, cisapride, arsenic, dolasetron, or methadone; current pregnancy; current hospitalization; symptomatic with fever or cough; lack of access to a smartphone

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxychloroquine<br>Randomization was 2:1 to HCQ 200 mg BID for 10 days | Drug: Hydroxychloroquine<br>* Randomization was 2:1 to HCQ 200 mg BID or 41 observation for 10 days<br>|
| No Intervention: Control<br>No Intervention | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19 symptom development with positive PCR test | The primary endpoint was development of COVID-19 symptoms with a positive coronavirus PCR test by Day 14. | within 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive coronavirus PCR test without symptoms | Development of a positive coronavirus PCR test without symptoms by Day 14 | By Day 14 (end of study) | 
| Hospital admission for COVID-19 | hospital admission for COVID-19 symptoms by Day 14 | within 14 days of study entry | 
| Death by Day 14 | Death due to COVID-19 within 14 days of study entry | within 14 days of study entry | 
| HCQ discontinuation or study withdrawal | All-cause discontinuation of study medication or study withdrawal by Day 14 | within 14 days of study entry | 
| Symptom severity at specified time points | overall symptom severity at Day 7 and Day 14 | at Day 7 and at Day 14 from study entry | 
| COVID -19 rate at study entry | household attack rate at study entry | Day 1 of study | 
| EKG changes during study | documentation of EKG changes such as QTc prolongation on HCQ compared with no drug therapy | Day 1 thru Day 14 of study |