double-blind study in COvid-19 patients with iveRmectin

JRCT ID: jRCT2031200120

Registered date:16/09/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: COVID-19
• Date of first enrollment: 08/10/2020
• Target sample size: 240
• Study type: Interventional

Intervention(s)

ivermectin group Ivermectin approximately 200microgram per kg administered as a single oral dose on day 1 (fasting state)
placebo group placebo without ivermectin as an ingredient, single oral administration on day 1 (fasting state)
on day 1 subjects take the study drug (3 mg tablet of ivermectin) or the control drug (ivermectin placebo tablet) at the dose of the study drug taken once per body weight of the subject.

Outcome(s)

• Primary Outcome: Period until the COVID-19 PCR test (SARS-CoV-2 nucleic acid detection) becomes negative

Secondary Outcome

1) Occurrence rate of cases in which the condition changed between Day1 and Day15 (evaluation by 7-point ordinal scale)
Ordinal scale;
1 No pneumonia, no restrictions on activities of daily living (PS0)
2 No pneumonia, limited daily activities (PS1 or higher)
3 With pneumonia, no oxygen inhalation
4 With pneumonia and oxygen inhalation
5 With non-invasive assisted ventilation or high-flow oxygen inhalation therapy
6 With artificial respiration management (including ECMO use)
7 Death"
Definition of change in medical condition; The following change in clinical condition is defined as change in medical condition.
(1) Change from 1 by two or more steps
(2) Change from 2 or 3 by one or more steps

Definition of pneumonia: A chest X-ray film or chest CT shows a shadow, and there is no obvious cause other than pneumonia such as heart failure.

Criteria for restricting activities of daily living; 0 is not restricted to activities of daily living and 1 or more is restricted to activities of daily living according to the following criteria."
"Table 11.2 ECOG (Eastern Cooperative Oncology Group) Performance Status (PS)

GRADE ECOG PERFORMANCE STATUS
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2 Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3 Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4 Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5 Dead
Source: Oken, M.M., et al., Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol, 1982. 5(6): p. 649-55.

Evaluator: The Principle investigator or sub-investigator in each facility will be the evaluator.
In order to unify the evaluation criteria, the evaluation method will be unified at the startup meeting."
2) Percentage of pneumonia on Day 15 and survival follow-up period
3) Percentage requiring oxygen inhalation
4) Percentage and number of days requiring artificial respiration management
5) Changes in body temperature up to Day 15
6) Negative rate of SARS-CoV-2 PCR up to Day15
7) All deaths until the end of the follow-up period
8) Percentage and number of days rescue treatment started up to Day 15
9) Percentage and number of days of severe arteriovenous thrombosis such as cerebral infarction and pulmonary thrombosis
10) Adverse events [Safety evaluation items: subjective findings (patient findings at the time of examination), vital signs (blood pressure, pulse rate, body temperature), adverse events observed in clinical laboratory values]
11) Number of days required for normalization of oxygen saturation in indoor air (SpO2>=95% lasting 24 hours) when oxygen inhalation was required
12) The number of cases in which clinical status (sequential scale) 3, 4 on Day 1 improved by more than one stage on Day 15"

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) A person who has been diagnosed with COVID-19 (including asymptomatic) by the COVID-19 PCR test (SARS-CoV-2 nucleic acid detection) within 3 days before the qualification test.
2) A person with oxygen saturation (SpO2) in the room air of 95% or more.
3) A person who are 20 years or older at the time of obtaining consent.
4) A person who weigh 40 kg or more at the time of qualification test.
5) A person who understands the content of this clinical trial and can obtain written consent to participate in the clinical trial.

Exclude criteria

1) A woman who is in lactation period or who may be pregnant, or those who do not agree to prevent pregnancy by medically appropriate means for up to 7 days after study drug administration.
Medically appropriate contraception means that using a combination of two or more of the following: not having sexual intercourse, taking surgical sterilization such as vasectomy or intrauterine device, taking oral contraceptive, using condom.
2) A person who has severe liver damage (AST or ALT at the time of qualification test is more than 3 times the upper limit of institutional standard and total bilirubin is more than twice the upper limit of institutional standard value), renal disorder (eGFR of eligibility test value 30 mL/min/1.73m2 or less).
3) A person with hypersensitivity to ivermectin.
4) A person with a history of severe drug allergies such as Stevens-Johnson syndrome, toxic epidermal necrolysis.
5) A person who has received the prohibited medication within the past month (within the past 6 months for biologics), or those who need to use the prohibited medication during the clinical trial period.
6) Those who are scheduled to receive SARS-CoV-2 vaccination from the date of consent to the end of the follow-up period.
7) A person who are currently participating in other clinical trials or who have participated in other clinical trials within 30 days before obtaining consent.
8) In addition, a person who is determined to be unsuitable as a subject of this clinical trial by the principal investigator."

Related Information

• Primary Sponsor: Yamaoka Kunihiro
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,Kitasato Institute