Coronavirus, Corona Virus Infection
Conditions
Brief summary
The proposed hypothesis is that high doses of hydroxychloroquine (HCQ) for at least 2 weeks can be effective antiviral medication both as a treatment in ambulatory patients and prophylaxis/treatment in health care workers because it impairs lysosomal function and reorganizes lipid raft (cholesterol and sphingolipid rich microdomains in the plasma membrane) content in cells, which are both critical determinants of Emerging Viral Disease (EVD) infection. This hypothesis is based on a growing literature linking chloroquine to antiviral activity. It is estimated that enough information exists to launch a clinical trial of hydroxychloroquine for COVID-19.
Detailed description
Sub-Study 1: COVID-19 patients in self-quarantine. Group 1: Hydroxychloroquine 400 mg bid (two 200 mg tablets taken twice a day; totaling 800 mg per day) for two weeks; Group 2: Placebo 2 pills twice a day for two weeks Sub-Study 2: Asymptomatic health care worker prophylaxis. Group 1: Hydroxychloroquine 600 mg once a day (three 200 mg tablets taken once a day) for up to 2 months; Group 2: Placebo 3 pills once a day for up to 2 months; cross-over from placebo to HCQ 600 mg once a day is allowed upon confirmatory diagnosis for COVID-19. PRIMARY OBJECTIVES: Sub-Study 1 (Patients tested for COVID-19 who meet symptomology and age requirements for eligibility): Rate of hospitalization Sub-Study 2 (Health Care Workers): Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months SECONDARY OBJECTIVES Sub-Study 1: Rate of secondary infection of co-inhabitants, adverse events, and negative for COVID-19 (confirmed by accepted testing methods) at 14 days Sub-Study 2: Number of shifts missed; rate of adverse events, and hospitalization at 2 months
Interventions
DRUGGroup 1 HCQ
Enrolled participants randomized in Group 1 receive the HCQ drug
DRUGGroup 2 Placebo
Enrolled participants randomized in Group 2 will receive a placebo drug
Sponsors
ProHealth Care Associates
University of Pennsylvania
UnitedHealth Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
For PATCH 2: participant and care provider are blinded. For PATCH 3: Health care worker is blinded.
Intervention model description
Treatment and prevention study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Able to give informed consent * Subjects meeting the following criteria by Sub-Study: Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine.Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment. Sub-Study 2: Currently employed as a health care worker. Health care workers are defined as : * Medical Doctor (MD) * Doctor of Osteopathic Medicine (DO) * Nurse Practitioner (NP) * Physician's Assistant (PA) * Registered Nurse (RN) * other members of the medical care team with significant COVID-19 exposure; Health care workers meeting the following criteria: * asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted); * scheduled for an average of \>20 hours per week of clinical care over the next 2 months. Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd. * Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log). * Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). * Participants must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. * Participants must have adequate baseline organ function
Exclusion criteria
* Inclusion Criteria * Able to give informed consent * Subjects meeting the following criteria by Sub-Study: Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine. Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment. Sub-Study 2: Currently employed as a health care worker (Medical Doctor, MD; Doctor of Osteopathic Medicine, DO; Nurse Practitioner, NP; Physician's Assistant, PA; and Registered Nurse, RN or other members of the medical care team with significant COVID-19 exposure); asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted); scheduled for an average of \>20 hours per week of clinical care over the next 2 months. Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd. * Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log). * Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2. * Participant must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. * Participant must have adequate baseline organ function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Substudy 1 - Number of COVID-19+ PCR Patients in Self-quarantine Who Are Hospitalized | Until completion of study, 29 to 31 days after beginning treatment. | Number of COVID-19+ PCR patients in self-quarantine who are hospitalized up to 31 days after beginning HCQ or Placebo |
| Sub Study 2:Number of Health Care Workers Testing Positive at 2 Months | Until completion of study, 2 months after start of treatment. | Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sub Study 2:Health Care Workers:Number of Shifts Missed | up to ~60 days after enrollment | Any work time missed because the participant experienced COVID-like symptoms during their active 2 month period |
| Sub Study 1 - Secondary Infection of Co-inhabitants of COVID-19 Positive PCR Patients in Self-quarantine | Until completion of study, 29 to 31 days after beginning treatment. | Co-inhabitants of COVID-19 positive PCR patients in self-quarantine that test positive up to 31 days after patient begins treatment with HCQ or Placebo |
| Sub Study 2:Health Care Workers:Rate of Hospitalization | Until completion of study, 2 months after start of treatment. | if the participant gets COVID and has severe symptoms and hospitalized, end point reached if before the end of the 2 month period |
| Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the ~60 Day Active Period | Until completion of study, 2 months (~60 days) after start of treatment. | Assessment of any medical events that occur during the \ 60 day active period that is felt to be related to receipt of HCQ |
| Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine | 15-17 days after completion of 14 day treatment | Rate of negative tests at end of treatment for COVID-19 positive PCR patients in self-quarantine |
Countries
United States
Participant flow
Recruitment details
Sub study 1 HCQ & Placebo groups were identified as patient at least 50 years old self-reported as having a fever within the last four days will undergo swab testing for COVID-19, and then sent home for a self-imposed quarantine that will end 14 days from the start of treatment and consenting patients were randomized. Sub study 2 HCQ and Placebo groups were recruited first through completion of an interest questionnaire then contacted by study PI or designee to assess eligibility consent.
Pre-assignment details
If Sub Study 1 patients received a negative PCR-test then they were considered no longer a part of the study and had a conversation with the PI or designee. Recruitment was done this way because early in the pandemic, time to receive PCR test results was unclear. At study conclusion 9 substudy 1 participants were Covid positive. 6 of those Covid positive participants completed the study. 30 participants from sub study 2 met eligibility criteria with 13 participants completing the full study.
Participants by arm
| Arm | Count |
|---|---|
| Substudy 1 Group 1 (HCQ) COVID-19 positive PCR patients aged 50-75 in self-quarantine randomized to this arm will be treated with hydroxychloroquine 400mg twice a day for 14 days. | 6 |
| Substudy 1 Group 2 (Placebo) COVID-19 positive PCR patients aged 50-75 in self-quarantine randomized to this arm will be treated with placebo 2 pills twice a day for 14 days. | 3 |
| Substudy 2 Group 1 (HCQ) Currently employed as a health care worker aged 18 or older. Must be asymptomatic and presumed negative for COVID-19.
Health care workers randomized into this arm will be treated with hydroxychloroquine 600 mg daily (three 200 mg tablets taken once a day) for 2 months. | 13 |
| Substudy 2 Group 2 (Placebo) Currently employed as a health care worker aged 18 or older. Must be asymptomatic and presumed negative for COVID-19.
Health care workers randomized into this arm will be treated with Placebo pills (three 200 mg tablets taken once a day) for 2 months. | 17 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 |
| Overall Study | Exposure Change | 0 | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 3 | 5 |
Baseline characteristics
| Characteristic | Substudy 1 Group 1 (HCQ) | Substudy 1 Group 2 (Placebo) | Substudy 2 Group 1 (HCQ) | Substudy 2 Group 2 (Placebo) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59 years | 58 years | 45 years | 49 years | 49 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 1 Participants | 13 Participants | 17 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 4 Participants | 0 Participants | 10 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 8 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 0 / 6 | 0 / 3 | 3 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 8 | 0 / 7 |
Outcome results
Primary
Substudy 1 - Number of COVID-19+ PCR Patients in Self-quarantine Who Are Hospitalized
Number of COVID-19+ PCR patients in self-quarantine who are hospitalized up to 31 days after beginning HCQ or Placebo
Time frame: Until completion of study, 29 to 31 days after beginning treatment.
Population: Evaluable for primary outcome, having completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sub Study 1 Group 1 (HCQ) | Substudy 1 - Number of COVID-19+ PCR Patients in Self-quarantine Who Are Hospitalized | 0 Participants |
| Sub Study 1 Group 2 (Placebo) | Substudy 1 - Number of COVID-19+ PCR Patients in Self-quarantine Who Are Hospitalized | 0 Participants |
Primary
Sub Study 2:Number of Health Care Workers Testing Positive at 2 Months
Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months
Time frame: Until completion of study, 2 months after start of treatment.
Population: Evaluable for primary outcome, having completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sub Study 1 Group 1 (HCQ) | Sub Study 2:Number of Health Care Workers Testing Positive at 2 Months | 0 Participants |
| Sub Study 1 Group 2 (Placebo) | Sub Study 2:Number of Health Care Workers Testing Positive at 2 Months | 0 Participants |
Secondary
Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine
Rate of negative tests at end of treatment for COVID-19 positive PCR patients in self-quarantine
Time frame: 1-3 days after completion of 14 day treatment
Population: Evaluable for primary outcome, having completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sub Study 1 Group 1 (HCQ) | Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine | 4 Participants |
| Sub Study 1 Group 2 (Placebo) | Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine | 0 Participants |
Secondary
Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine
Rate of negative tests at end of treatment for COVID-19 positive PCR patients in self-quarantine
Time frame: 15-17 days after completion of 14 day treatment
Population: Evaluable for primary outcome, having completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sub Study 1 Group 1 (HCQ) | Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine | 6 Participants |
| Sub Study 1 Group 2 (Placebo) | Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine | 0 Participants |
Secondary
Sub Study 1 - Secondary Infection of Co-inhabitants of COVID-19 Positive PCR Patients in Self-quarantine
Co-inhabitants of COVID-19 positive PCR patients in self-quarantine that test positive up to 31 days after patient begins treatment with HCQ or Placebo
Time frame: Until completion of study, 29 to 31 days after beginning treatment.
Population: Co-inhabitants of patients evaluable for primary outcome, who completed the study. There were 16 co-inhabitants of the Sub study 1 Group 1 (HCQ).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sub Study 1 Group 1 (HCQ) | Sub Study 1 - Secondary Infection of Co-inhabitants of COVID-19 Positive PCR Patients in Self-quarantine | 0 Participants |
| Sub Study 1 Group 2 (Placebo) | Sub Study 1 - Secondary Infection of Co-inhabitants of COVID-19 Positive PCR Patients in Self-quarantine | 0 Participants |
Secondary
Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the ~60 Day Active Period
Assessment of any medical events that occur during the \ 60 day active period that is felt to be related to receipt of HCQ
Time frame: Until completion of study, 2 months (~60 days) after start of treatment.
Population: Evaluable for primary outcome, having completed the study or removed from study due to moderate or more serious adverse event
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sub Study 1 Group 1 (HCQ) | Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the ~60 Day Active Period | moderate adverse events | 2 Participants |
| Sub Study 1 Group 1 (HCQ) | Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the ~60 Day Active Period | minor adverse events | 1 Participants |
| Sub Study 1 Group 2 (Placebo) | Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the ~60 Day Active Period | moderate adverse events | 0 Participants |
| Sub Study 1 Group 2 (Placebo) | Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the ~60 Day Active Period | minor adverse events | 0 Participants |
Secondary
Sub Study 2:Health Care Workers:Number of Shifts Missed
Any work time missed because the participant experienced COVID-like symptoms during their active 2 month period
Time frame: up to ~60 days after enrollment
Population: We had no positive Covid-19 tests for Sub Study 2 healthcare workers so we couldn't measure this outcome.
Secondary
Sub Study 2:Health Care Workers:Rate of Hospitalization
if the participant gets COVID and has severe symptoms and hospitalized, end point reached if before the end of the 2 month period
Time frame: Until completion of study, 2 months after start of treatment.
Population: Evaluable for primary outcome, having completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sub Study 1 Group 1 (HCQ) | Sub Study 2:Health Care Workers:Rate of Hospitalization | 0 Participants |
| Sub Study 1 Group 2 (Placebo) | Sub Study 2:Health Care Workers:Rate of Hospitalization | 0 Participants |