IPF
Conditions
Interventions
Mirtazapine+Nacodine combination group (N=50): Mirtazapine 3.75mg+Nacodine 20mg oral QN, treatment for 24 weeks:Mirtazapine+Nacodine combination group (N=50): Mirtazapine 3.75mg+Nacodine 20mg oral QN,
Mirtazapine single drug group (N=25): Mirtazapine 3.75mg+Nacodine placebo 2 tablets oral QN, 24 weeks of treatment :Mirtazapine single drug group (N=25): Mirtazapine 3.75mg+Nacodine placebo 2 tablets
Nacodine single drug group (N=25): 1 capsule of mirtazapine placebo+20mg of Nacodine oral QN, 24 weeks of treatment:Nacodine single drug group (N=25): 1 capsule of mirtazapine placebo+20mg of Nacodine
Sponsors
China-Japan Friendship Hospital
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Inclusion criteria
Inclusion criteria: Subjects meeting all of the following criteria were eligible for inclusion in this trial. 1. Signed informed consent prior to the trial and able to complete the study in accordance with the requirements of the trial protocol. 2. IPF patients were between 40 and 80 years old when signing the informed consent form (including the boundary value); 3. Subjects must be diagnosed as IPF (see Appendix 1) according to the International Diagnostic Guidelines of ATS/ERS/JRS/ALAT (2022) and/or the Chinese Expert Consensus on the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis (2016) before screening and obtain the confirmation of the independent film reader set up in this trial *; Note: * Establish a third-party independent film reading agency to confirm the diagnosis of all IPF subjects (the confirmation period is about 7 working days) 4. At the time of screening, subjects must also meet one of the following two criteria. 1) The treated patients stabilized the treatment dose before screening (the dose of Nidanib = 200mg/day, or the dose of Pirfenidone = 1200mg/day) = 8 weeks, and planned to continue to receive the background treatment after randomization; It is not allowed to accept the combined treatment of Nidanib+Pirfenidone; 2) Those who are not receiving nidanib or pirfenidone at the time of screening are also not planning to start or restart antifibrotic therapy throughout the study period (if discontinued for any reason, nidanib or pirfenidone therapy will need to be discontinued for = 4 weeks prior to screening); and 5. At the time of screening. 1) FVC% estimated value = 45%; 2) DLCO (HB correction) estimated value = 35%; 3) First second forced expiratory volume FEV 1 /FVC = 0.7; 4) During the 6-minute walk test (6MWT, see the 6-minute walk test standard operating procedure for details), the minimum 6-minute walk distance (6MWD) is 150 meters; 5) The chest HRCT results support the diagnosis of IPF, and the degree of fibrosis in the latest HRCT is greater than that of emphysema; Note: If there is no HRCT within 3 months before screening, the examination can be completed in the screening period; And submit it to the Film Reading Center for evaluation 6. Male subjects (if their female partner is of childbearing potential) or female subjects of childbearing potential voluntarily use effective contraception from screening until 4 weeks after the last dose of study drug (see Appendix 2).
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria may not be included in this trial. 1. A history of severe life-threatening allergic reactions such as anaphylaxis, or if the investigator suspects that the person is allergic to the active ingredient of the study drug or its excipients. 2. ILD of other known causes (such as interstitial pneumonia secondary to connective tissue disease, drug-related interstitial pneumonia, pneumoconiosis, allergic pneumonia and radiation pneumonia); 3. Respiratory infections (viral pneumonia, bacterial pneumonia, mycoplasma pneumonia, etc.) within 4 weeks prior to and at the time of screening. 4. Patients with acute exacerbation of IPF 3 months before screening or at screening; 5. Patients who, for various reasons, are unable to cooperate with or complete examinations related to ventilation and diffusion function, including those whose lung function indexes meet the criteria for enrolment after the use of bronchodilators during the screening period. 6. Those who have had major trauma or major surgery within three months prior to screening (as assessed by the investigator); or those who are scheduled to undergo surgery during the study period, e.g., patients preparing for lung transplantation or lung reduction surgery. 7. Significant clinical abnormal ECG manifestations during screening, including QTcF interval extension>450ms for male subjects and>470ms for female subjects; 8. Patients with myocardial infarction or unstable angina pectoris (within 6 months), NYHA class III or IV cardiac function (Appendix 3), active pulmonary tuberculosis, etc. at the time of screening affect the participants as judged by the investigator; 9. Active hepatitis B, hepatitis C virus infection, HIV antigen/antibody positive, syphilis spirochete specific antibody (TP-PA) positive or syphilis rapid plasma reagin (RPR) positive; 10. Laboratory Tests. 1) Aspartate aminotransferase (AST)>2.5 × ULN or alanine aminotransferase (ALT)>2.5 × ULN; 2) Serum total bilirubin>1.5 × ULN; 3) Hemoglobin<60g/L; 4) Glomerular filtration rate = 45ml/min/1.73m 2 (calculated by CKD-EPI formula, Appendix 4); 11. History of drug dependence or drug abuse. 12. Have a history of continuous alcohol abuse in the three years before screening (drinking more than 14 units of alcohol every week: about 10ml of alcohol per unit, or 285ml of beer (3.5%), or 25ml of spirits (40%), or 100ml of wine (10%)); 13. Compromised immune system at the time of screening (including patients whose cancer has progressed or recurred, or who have been treated with systemic systemic steroids* or other immunosuppressive agents** within 3 months prior to screening). Note: * Systemic steroids include but are not limited to hydrocortisone, prednisone, nilestriol, methylprednisolone, fluorohydrocortisone, short-term systemic steroids, short-term drugs = 3 days, long-term drugs = 2 days are not included** Other immunosuppressants include but are not limited to cyclophosphamide, azathioprine, methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, TNF-a antagonist, JAK inhibitor, colchicine, etc; Systematic treatment does not include topical medication, such as eye, nose, ear or inhalation. 14. Combination of other malignancies or history of other malignancies within 5 years prior to screening (except cured basal or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix); and 15. (b) A combination of well-defined psychiatric symptoms or central nervous system disord
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| After 24 weeks of combined treatment with mirtazapine and nacodine, the forced vital capacity FVC [ml] * changes from the baseline absolute value.; | — |
Secondary
| Measure | Time frame |
|---|---|
| At 12 and 24 weeks of treatment, the estimated value of FVC% changed from the absolute value of the baseline;;At 12 and 24 weeks of treatment, the estimated value of FVC% changed from the baseline relative value;;The proportion of subjects whose estimated absolute value of FVC% decreased by more than 5% and 10% from baseline after 12 and 24 weeks of treatment;;The proportion of subjects whose estimated absolute value of FVC% decreased by more than 10% from baseline or died after 12 and 24 weeks of treatment;;After 24 weeks of treatment, the quantitative analysis of pulmonary fibrosis by high-resolution computed tomography (HRCT) was compared with the baseline;;After 24 weeks of treatment, the absolute and relative values of lung carbon monoxide diffusion capacity (DLCO) (HB correction) were changed from the baseline;;After 24 weeks of treatment, the estimated value of DLCO% changed from the absolute value and relative value of baseline;;After 12 and 24 weeks of treatment, the proportion of subjects whose estimated value of DLCO% is more than 10% and 15% lower than the baseline;;Change of 6-minute walking distance (6MWD) from baseline at 12 and 24 weeks of treatment;;The change of cough visual analogue score (VAS) from baseline at 12 and 24 weeks of treatment;;After 12 and 24 weeks of treatment, the change compared with the total score of pulmonary fibrosis (L-PF) questionnaire;;After 12 and 24 weeks of treatment, the change from baseline to the total symptom score and each symptom score of the pulmonary fibrosis (L-PF) symptom questionnaire;;After 12 and 24 weeks of treatment, the changes of the total impact score and each impact score of the pulmonary fibrosis (L-PF) impact questionnaire from the baseline;;The time from the treatment period to the first IPF related hospitalization * or death;;Percentage of subjects with acute exacerbation of IPF leading to hospitalization, lung transplantation or death after 12 and 24 weeks of treatment.; | — |
Countries
China
Contacts
Public ContactHuaping Dai
China-Japan Friendship Hospital
Outcome results
None listed