Treatment of Pulmonary Fibrosis Due to COVID-19 With Fuzheng Huayu

• ClinicalTrials.gov Identifier: NCT04279197
• Recruitment Status: Completed
• First Posted: February 21, 2020
• Last Update Posted: January 3, 2022
• Sponsor: ShuGuang Hospital
• Collaborators: Hubei Hospital of Traditional Chinese Medicine; Jingmen No.1 People's Hospital; Wuhan No.1 Hospital; Wuhan Third Hospital; Huangshi Hospital of Traditional Chinese Medicine
• Information provided by (Responsible Party): Liu Chenghai, ShuGuang Hospital

Tracking Information

• First Submitted Date: February 15, 2020
• First Posted Date: February 21, 2020
• Last Update Posted Date: January 3, 2022
• Actual Study Start Date: April 23, 2020
• Actual Primary Completion Date: March 24, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 12, 2021)

• The improvement proportion of pulmonary fibrosis [ Time Frame: Week 24 ]
  Evaluation of pulmonary fibrosis Improvement. pulmonary fibrosis judged by HRCT score.HRCT images are divided into four grades according to the score, and a reduction of one grade is an improvement.
• The improvement of lung function [ Time Frame: Week 24 ]
  FVC, FEV1, FVC/FEV1

Original Primary Outcome Measures (submitted: February 19, 2020)

• High-resolution computed tomography (HRCT) score [ Time Frame: Week 24 ]
  Evaluation of Pulmonary fibrosis Improvement. HRCT images are graded from 1 to 6, higher scores mean a worse outcome.
• Lung function including FVC, FVC as a percentage of projected value and DLco [ Time Frame: Week 24 ]
  Evaluation of Lung Function Improvement

Current Secondary Outcome Measures (submitted: December 12, 2021)

• The improvement proportion of pulmonary inflammation [ Time Frame: Week 24 ]
  Evaluation of pulmonary inflammation Improvement
• The improvement proportion of clinical symptom [ Time Frame: Week 24 ]
  Discomfort symptoms include dyspnea, cough, exhausted, fatigue, insomnia, sweating, poor appetite, diarrhea, etc., which are common manifestations of patients with COVID-19
• Quality of Life-BREF (QOL-BREF) [ Time Frame: Week 24 ]
  This scale can reflect the quality of life of patients to some extent.
• Patient Health Questionnaire-9(PHQ-9) [ Time Frame: Week 24 ]
  This scale can reflect the quality of life of patients to some extent.
• Generalized anxiety disorder-7(GAD-7) [ Time Frame: Week 24 ]
  This scale can reflect the quality of life of patients to some extent.
• The 6-minute walk distance [ Time Frame: Week 24 ]
  Evaluation of Lung Function Improvement

Original Secondary Outcome Measures (submitted: February 19, 2020)

• Times of acute exacerbation [ Time Frame: Week 24 ]
  Times of acute exacerbations during treatment
• Six-minute walk distance [ Time Frame: Week 24 ]
  Measured by a 6-minute walking test
• Dyspnea Scores [ Time Frame: Week 24 ]
  Using the scale revised by British modified Medical Research Council (MMRC) which divided patients into five degrees.Higher scores mean a worse outcome.
• Composite physiological index [ Time Frame: Week 24 ]
  Evaluation of Pulmonary fibrosis Improvement on CT which is calculated by formula.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment of Pulmonary Fibrosis Due to COVID-19 With Fuzheng Huayu
• Official Title: Efficacy and Safety of Fuzheng Huayu Tablets in Post-COVID-19 Patients With Pulmonary Inflammation and Fibrosis : A Multicenter Double-blind Randomized Controlled Trial
• Brief Summary: According to previous studies, viral pneumonia can develop into pulmonary fibrosis, which can affect patients'lung function and even life health.This study aims to observe the efficacy and safety of Fuzheng Huayu Tablets in the treatment of pulmonary fibrosis after COVID-19.

Detailed Description

The patients with COVID-19 could suffered from the pulmonary dysfunction and/or fibrosis the recovery period, but there are no certain drugs or treatment to cope with this situation. Our previous studies indicated that Fuzheng Huayu tablets (FZHY) could regress the lung fibrosis induced by bleomycin in animals, and improve the pulmonary function in the patients with chronic obstructive pulmonary disease. Now we design this trial to carry out the clinical study in order to evaluate the effects of Fuzheng Huayu tablets on pulmonary fibrosis and/or pulmonary function injury in the recovery period of COVID-19 and expect to improve the prognosis.

This is a randomized, double-blind, multicenter, placebo-controlled clinical trial.It enrolls 142 patients who had been diagnosed with COVID-19, but currently they are negative for viral testing and have developed pulmonary fibrosis or pulmonary dysfunction. They are randomly assigned into Placebo group and FZHY group. All patients are given usual treatment such as respiratory function rehabilitation training and vitamin C. The FZHY group is given Fuzheng Huayu tablets, and the control group is given placebo. Each patient will be observed for 24 weeks and followed up for 8 weeks. The primary outcomes for the trial are the improvement proportion of pulmonary fibrosis judged by HRCT score and the improvement of lung function(FVC,FEV1,FVC/FEV1). Secondary outcomes include six-minute walk distance, improvement proportion of pulmonary inflammation, improvement proportion of clinical symptoms , quality of Life-BREF (QOL-BREF) Score, patient health questionnaire-9 (PHQ-9) Score, general anxiety disorder-7 (GAD-7) score. The safety also be observed.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Pulmonary Fibrosis Due to COVID-19

Intervention

• Drug: Fuzheng Huayu Tablet
  FZHY, administration: 0.4g/tablet, 1.6g/time, 3 times/day, oral; administered half an hour after the meal.
  Other Name: FZHY
• Drug: Vitamin C tablets
  Vitamin C tablets, administration: 0.2g/time, 3 times/ day, oral；
  Other Name: VC
• Drug: Placebo
  Placebo , administration: 0.4g/tablet, 1.6g/time, 3 times/day, oral; administered half an hour after the meal.
• Other: respiratory function rehabilitation training
  Health exercise, once a day

Study Arms

• Experimental: FZHY Group

  usual treatment (respiratory function rehabilitation training + Vitamin C tablets)

  • Fuzheng Huayu tablets
  Interventions:

  • Drug: Fuzheng Huayu Tablet
  • Drug: Vitamin C tablets
  • Other: respiratory function rehabilitation training
• Placebo Comparator: Placebo Group

  usual treatment (respiratory function rehabilitation training + Vitamin C tablets)

  • placebo
  Interventions:

  • Drug: Vitamin C tablets
  • Drug: Placebo
  • Other: respiratory function rehabilitation training

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 12, 2021): 142
• Original Estimated Enrollment (submitted: February 19, 2020): 136
• Actual Study Completion Date: March 24, 2021
• Actual Primary Completion Date: March 24, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria (I) Discharged patients fulfilling the diagnostic criteria of COVID-19 (China Diagnosis and Treatment Protocol for COVID-19 (Trial Version 7); (II) COVID-19 RNA in respiratory specimens or blood specimens of patients is negative (>2 times), assayed by real-time fluorescent polymerase chain reaction test (RT-PCR); (III) Pulmonary CT scans within 7 days showed that there were still unabsorbed inflammation or pulmonary fibrosis in the lungs; (IV) Age 18-70.

Exclusion criteria

• Patients who have undergone lung surgery that affects pulmonary function, such as pulmonary transplantation, pulmonary resection, pulmonary volume reduction, etc;
• Relying on mechanical ventilation to maintain pulmonary function, such as ventilators;
• Combined with chronic pulmonary diseases affecting pulmonary function, such as chronic obstructive pulmonary disease, other known causes of interstitial pulmonary disease;
• Patients with diseases affecting cardiac function, such as pulmonary circulation hypertension, heart failure, peripheral vascular disease, fibromyalgia, and pacemaker installation;
• Patients with severe underlying diseases affecting survival, including uncontroled cardiac, renal, digestive, hematological, neuropsychiatric, immune, metabolic diseases, malignant diseases and severe malnutrition;
• Resting heart rate >120 times/min;
• Systolic blood pressure > 180 mmHg, diastolic blood pressure > 100 mmHg;
• Unstable angina pectoris or myocardial infarction occurring within the last month;
• Severe obesity (BMI > 30 kg/m2);
• Allergic constitution, allergic to the drug components involved in the treatment program;
• Pregnant or breastfeeding women;
• Patients with disabilities who are unable to complete the efficacy evaluation questionnaires;
• Difficult collaborators with poor mental health status, suffering from mental illness, patients without self-control, unable to express clearly;
• Those who are participating in other clinical trials;
• According to the investigator's judgment, patients whose enrollment complications or poor compliance will affect the efficacy and safety evaluation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04279197
• Other Study ID Numbers: Fzhy-ncp-2
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Liu Chenghai, ShuGuang Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: ShuGuang Hospital
• Original Study Sponsor: Same as current

Collaborators

• Hubei Hospital of Traditional Chinese Medicine
• Jingmen No.1 People's Hospital
• Wuhan No.1 Hospital
• Wuhan Third Hospital
• Huangshi Hospital of Traditional Chinese Medicine

Investigators

• Study Director: Chenghai Liu; Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine

• PRS Account: ShuGuang Hospital
• Verification Date: December 2021