Covid19, Progression
Conditions
Keywords
COVID-19, viral clearance, , mild infection, disease progression, trial, HCQ
Brief summary
Brief Summary: Purpose of this study is to evaluate efficacy of hydroxychloroquine (HCQ) in reducing progression of Corona Virus Disease 2019 (COVID - 19) and achieving viral clearance. Condition or disease :I COVID-19 ntervention/treatment :Drug: Hydroxychloroquine Sulfate Phase: Phase III
Detailed description
This study explores efficacy of HCQ (400mg BD on D0 and 200mg BD D1-D5) in reducing progression of Mild Covid-19 patients and decreasing viral load. Participants of study will be randomized 2:1 to receive either Active drug or standard of care (SOC) treatment respectively. We aim to demonstrate reduced COVID-19 progression and early viral clearance in individuals on HCQ therapy.
Interventions
DRUGHCQ
Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days
Sponsors
Pak Emirates Military Hospital
UNICEF
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Neither patients, nor investigators, nor statisticians were masked to treatment assignment. Lab staff who performed sampling for PCR, basic blood tests and other routine measurement were unaware of treatment information.
Intervention model description
Randomization rules were designed by Dr. Wasim Alamgir together with principal investigators and implemented by an independent statistician who was not involved in data analysis. Stratified random sampling was applied to stratify all eligible patients according to age, gender and comorbidities. Computerized random number generator was used and allocation was done in 2:1 sequence. Cards with each group assignment number randomly generated by computer were placed in sequentially numbered envelopes that were opened as the patients were enrolled
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Mild Corona virus disease (COVID-19) * PCR confirmed infection * Hospital admitted patients
Exclusion criteria
* Moderate, severe and critical COVID-19 * day 0 CRP greater than 6mg/dl, ALC \< 1000 or evidence of infiltrates on X-ray chest * comorbidity with life expectancy less than 6 months * Contraindications to HCQ therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression | 5 days | After start of treatment, development of fever \> 101 F for \> 72 hours, shortness of breath by minimal exertion (10-Step walk test), derangement of basic lab parameters (ALC \< 1000 or raised CRP) or appearance of infiltrates on CXR during course of treatment was labeled as progression irrespective of PCR status |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viral Clearance | 14 days | PCR negativity on day 7 and 14 after admission |
Countries
Pakistan
Participant flow
Recruitment details
Enrollment during 10th April to 31st May 2020 at department of Pulmonology, Pakistan Emirates Military Hospital (PEMH) Pakistan.
Pre-assignment details
672 confirmed PCR positive cases were assessed for eligibility. 132 did not meet selection criteria and excluded.Later,15 withdrew consent and 5 became symptomatic. During follow up 13 patients were found to be deviated from advised therapy and 7 were lost to follow up yielding a final study population of 500.
Participants by arm
| Arm | Count |
|---|---|
| Supportive Arm Patients selected in supportive arm will be given standard doses of oral Vit C, Vit D, Zinc and panadol | 180 |
| HCQ Arm Patients selected in experimental arm will be given standard doses of tab HCQ in addition to supportive treatment. side effects will be monitored
HCQ: Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days | 360 |
| Total | 540 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | developed fever > 3 days | 4 | 1 |
| Overall Study | Lost to Follow-up | 4 | 3 |
| Overall Study | Protocol Violation | 11 | 2 |
| Overall Study | Withdrawal by Subject | 10 | 5 |
Baseline characteristics
| Characteristic | HCQ Arm | Total | Supportive Arm |
|---|---|---|---|
| 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 | 360 Participants | 540 Participants | 180 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Pakistan | 360 participants | 540 participants | 180 participants |
| Sex: Female, Male Female | 24 Participants | 34 Participants | 10 Participants |
| Sex: Female, Male Male | 336 Participants | 506 Participants | 170 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 151 | 0 / 349 |
| other Total, other adverse events | 0 / 151 | 0 / 349 |
| serious Total, serious adverse events | 0 / 151 | 0 / 349 |
Outcome results
Primary
Number of Participants With Progression
After start of treatment, development of fever \> 101 F for \> 72 hours, shortness of breath by minimal exertion (10-Step walk test), derangement of basic lab parameters (ALC \< 1000 or raised CRP) or appearance of infiltrates on CXR during course of treatment was labeled as progression irrespective of PCR status
Time frame: 5 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SOC) | Number of Participants With Progression | 5 Participants |
| Intervention Group | Number of Participants With Progression | 11 Participants |
Secondary
Viral Clearance
PCR negativity on day 7 and 14 after admission
Time frame: 14 days