Trial Outcomes & Findings for Novel Agents for Treatment of High-risk COVID-19 Positive Patients (NCT NCT04374019)

NCT ID: NCT04374019

Last Updated: 2022-01-20

Results Overview

Number of patients experiencing clinical deterioration. Clinical deterioration is defined as a less than a 2-point change from the initial COVID 7-Point Ordinal Outcomes Scale within 14 days from the study start. This scale ranges from 1-7. Lower scores indicate worse outcomes (death); higher scores indicate fewer symptoms and better outcomes.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 13 participants
• Primary outcome timeframe: 14 days
• Results posted on: 2022-01-20

Participant Flow

Recruitment period 5/1/2020 to 11/23/2020; Study on hold for most of 2021, terminated in early 2022 due to low accrual

Participant milestones

Measure	Arm A - Hydrozychloroquine Hydroxychloroquine 600 mg daily Days 1-14	Arm B - Hydroxychloroquine + Azithromycin Hydroxychloroquine 600 mg daily Days 1-14 \+ Azithromycin 500 mg Day 1; 250 mg daily Days 2-5	Arm C - Ivermectin Ivermectin 12-15- mg (weight based) on Day 1 and 2	Arm D - Camostat Camostat 200mg TID Days 1-14
Overall Study STARTED	1	1	6	5
Overall Study COMPLETED	1	1	5	5
Overall Study NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Novel Agents for Treatment of High-risk COVID-19 Positive Patients

Baseline characteristics by cohort

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=6 Participants Ivermectin Ivermectin: Ivermectin: Days 1-2: Weight \< 75kg: 4 tabs (12 mg total daily dose) Days 1-2: Weight \> 75kg: 5 tabs (15 mg total daily dose)	Arm D n=5 Participants Camostat Mesilate Camostat Mesilate: Days 1-14: 2 tab TID after a meal (600 mg total daily dose)	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	13 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	1 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants	5 participants n=4 Participants	13 participants n=21 Participants

PRIMARY outcome

Timeframe: 14 days

Population: 1 subject was inevaluable in Arm C. No subjects clinically deteriorated as defned above

Number of patients experiencing clinical deterioration. Clinical deterioration is defined as a less than a 2-point change from the initial COVID 7-Point Ordinal Outcomes Scale within 14 days from the study start. This scale ranges from 1-7. Lower scores indicate worse outcomes (death); higher scores indicate fewer symptoms and better outcomes.

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Clinical Deterioration	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 40 days

Population: study terminated due to low accrual, no subjects analyzed for this outcome.

The change in (clearance of) viral RNA will be measured by PCR testing at days 1, 14, 28, and 40 days.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28 days

Number of patients that experienced severe respiratory or other organ failure.

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Rate of Organ Failure	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 28 days

Percentage of patients requiring ICU admission or ventilation.

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Progression to ICU Care or Ventilation	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 14 days

Number of participants who died or had greater than a 2-point decrease in COVID 7-Point Ordinal Outcomes Scale from Day to Day 14.

COVID 7-point ordinal outcomes scale:

1. Death

2. Hospitalized on invasive mechanical ventilation or ECMO

3. Hospitalized on non-invasive ventilation or high flow nasal cannula

4. Hospitalized on supplemental oxygen

5. Hospitalized not on supplemental oxygen

6. Not hospitalized with limitation in activity (continued symptoms)

7. Not hospitalized without limitation in activity (no symptoms)

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Number of Participants Who Had a Change in Clinical Status Measured by Decrease in COVID 7-point Ordinal Scale	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 14 days

Percentage of patients who have died by day 14.

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Mortality	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 14 days

Percentage of patients experiencing severe adverse events, defined as grade 3 non-hematologic or greater by DMID Toxicity Scale for Determining Severity of Adverse Events.

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Rate of Severe Adverse Events	1 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 28 days

Number of patients that required oxygen supplementation during study treatment Days 1-28

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Number of Patients That Required Oxygen Supplementation	1 Participants	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 28 days

Number of patients that required mechanical ventilation during the study period. Days 1-28

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Number of Patients That Required Mechanical Ventilation	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 28 days

Number of patients who required vasopressor treatment Days 1 to 28

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Number of Patients Who Required Vasopressors	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 28 days

Number of patients who required ICU services during study treatment Days 1-28.

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Number of Patients Who Required ICU Services	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 28 days

Number of patients that required hospitalization during study treatment

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Number of Patients That Required Hospitalization	0 Participants	0 Participants	4 Participants	4 Participants

SECONDARY outcome

Timeframe: 28 days

Proportion of patients with significant changes in ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes, or abnormalities including severe QTc prolongation of > 500 ms.

Outcome measures

Measure	Arm A n=1 Participants Hydroxychloroquine	Arm B n=1 Participants Hydroxychloroquine + Azithromycin	Arm C n=5 Participants Ivermectin	Arm D n=5 Participants Camostat
Heart Function	0 Participants	0 Participants	1 Participants	0 Participants

Adverse Events

Arm A

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm B

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Arm C

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Arm D

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm A n=1 participants at risk Hydroxychloroquine	Arm B n=1 participants at risk Hydroxychloroquine + Azithromycin	Arm C n=5 participants at risk Ivermectin	Arm D n=5 participants at risk Camostat
Blood and lymphatic system disorders anemia	100.0% 1/1 • Number of events 1 • AEs were collected from study entry until Day 28.	0.00% 0/1 • AEs were collected from study entry until Day 28.	0.00% 0/5 • AEs were collected from study entry until Day 28.	0.00% 0/5 • AEs were collected from study entry until Day 28.
Cardiac disorders supraventricular tachycardia	0.00% 0/1 • AEs were collected from study entry until Day 28.	0.00% 0/1 • AEs were collected from study entry until Day 28.	20.0% 1/5 • Number of events 1 • AEs were collected from study entry until Day 28.	0.00% 0/5 • AEs were collected from study entry until Day 28.

Other adverse events

Measure	Arm A n=1 participants at risk Hydroxychloroquine	Arm B n=1 participants at risk Hydroxychloroquine + Azithromycin	Arm C n=5 participants at risk Ivermectin	Arm D n=5 participants at risk Camostat
Gastrointestinal disorders mucositis	0.00% 0/1 • AEs were collected from study entry until Day 28.	0.00% 0/1 • AEs were collected from study entry until Day 28.	20.0% 1/5 • Number of events 1 • AEs were collected from study entry until Day 28.	0.00% 0/5 • AEs were collected from study entry until Day 28.
Gastrointestinal disorders GERD	0.00% 0/1 • AEs were collected from study entry until Day 28.	100.0% 1/1 • Number of events 1 • AEs were collected from study entry until Day 28.	0.00% 0/5 • AEs were collected from study entry until Day 28.	0.00% 0/5 • AEs were collected from study entry until Day 28.
Ear and labyrinth disorders tinnitus	0.00% 0/1 • AEs were collected from study entry until Day 28.	100.0% 1/1 • Number of events 1 • AEs were collected from study entry until Day 28.	0.00% 0/5 • AEs were collected from study entry until Day 28.	0.00% 0/5 • AEs were collected from study entry until Day 28.

Additional Information

Susanne Arnold MD

University of Kentucky

Phone: 8592579568

Email: smarno0@uky.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place