A Placebo-Controlled, Double-Blind, Phase II Physician-Initiated Trial of TM5614, a PAI-1 Inhibitor, for the Treatment of SARS-CoV-2 Pneumonia
A Placebo-Controlled, Double-Blind, Phase II Physician-Initiated Trial of TM5614 in Patients with SARS-CoV-2 Pneumonia
Harigae Hideo
Tohoku University Hospital
1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi
+81-22-717-7162
harigae@med.tohoku.ac.jp
Takashi Dan
Tohoku University
1-1 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi
+81-22-717-8158
dantks@med.tohoku.ac.jp
Not Recruiting
June. 10, 2021
June. 24, 2021
100
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
1. Inpatients 20 years or over obtained by written consent
2. Patients who are positive for COVID-19 by PCR or other methods based on gene amplification or antigen testing
3. Patients with a finding consistent with novel coronavirus pneumonia on chest CT examination
4. Patients with room air SpO2 <96% at rest
5. Patients who require less than 5 L/min oxygen concentration
6. Patients who are not on a ventilator
7. Patients whose AST or ALT value is 2.5 times or less than the institutional upper limit
8. Patients whose total bilirubin level is 2.5 times or less than the institutional upper limit
9. Patients with creatinine clearance (calculated by Cockcroft-Gault formula) of 30 mL/min or more
1. Patients on home oxygen therapy.
2. kidney disease patients undergoing dialysis treatment.
3. Patients with a history or complications of malignant tumors(except for those with no recurrence or new onset for at least 5 years after treatment).
4. Patients with cirrhosis(Child-Pugh score class B and C).
5. Pregnant or lactating patients.
6. Patients who have participated in or are currently participating in other clinical trials within 30 days prior to enrollment in this clinical trial.
7. Patients with bleeding tendency(Intracranial bleeding, Gastrointestinal hemorrahage, Urinary tract bleeding, Retroperitoneal hemorrhage, Hemoptysis).
8. Patients with a high risk of bleeding, including:
Patients with a history of intracranial hemorrhage or a predisposition to hemorrhage such as intracranial tumor, arteriovenous malformation, or aneurysm.
Patients with a history of cerebral infarction(within 3 months).
Patients who have undergone intracranial or spinal surgery or injury(within 3 months).
Patients with a history of gastrointestinal or urinary tract bleeding(within 21 days).
Patients who have undergone major surgery(within 14 days).
Patients with a platelet count of less than 100000/mm3 before administration of study drug.
Patients with severe hypertension.
9. Patients on anticoagulants and other concomitantly prohibited drugs that are difficult to discontinue.
10. Patients judged by the investigator or co-investigator to be inappropriate for other reasons.
20age old over
No limit
Both
novel coronavirus (SARS-CoV-2) pneumonia
Two tablets of TM5614 (120 mg) or placebo will be administered once daily, and the dose may be increased to 3 tablets at the physician's discretion. However, on Day 7, if bleeding symptoms or hepatic dysfunction are observed, or if increasing the dose to 3 tablets (180 mg) seems impossible, continue with 2 tablets (120 mg). The duration of study drug administration will be 14 days.
1. Survival after 28 days of treatment with study drug
2. Length of hospital stay after initiation of study drug
3. Days of oxygen administration required after initiation of study drug
4. Change in P/F ratio (PaO2 /FiO2) between enrollment and day 7 of study drug administration
5. Change in the percentage of lung field lesions on CT chest images before and after treatment with the study drug
6. Percentage of cases with Oxygenation Index Scale of 4 or higher
7. Change in D-dimer at enrollment and on day 7 of study drug administration
8. Percentage of cases with clinical thrombosis (deep vein thrombosis, cerebral infarction, myocardial infarction, etc.)
9. Percentage of cases requiring anticoagulation therapy such as heparin
10. Total Oxygenation Index Scale corrected by 4C Deterioration model
11. Efficacy assessment using NIAID's 7-point ordinal scale
Japan Agency for Medical Research and Development
Not applicable
Institutional Review Board of Tohoku University Hospital
