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

Efficacy and Safety of Fuzheng Huayu Tablets in Post-COVID-19 Patients With Pulmonary Inflammation and Fibrosis : A Multicenter Double-blind Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Fibrosis Due to COVID-19
• Intervention / Treatment: Drug: Fuzheng Huayu Tablet; Drug: Vitamin C tablets; Other: respiratory function rehabilitation training; Drug: Placebo

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
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201203
      • ShuGuang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FZHY Group; usual treatment (respiratory function rehabilitation training + Vitamin C tablets); Fuzheng Huayu tablets	Drug: Fuzheng Huayu Tablet; FZHY, administration: 0.4g/tablet, 1.6g/time, 3 times/day, oral; administered half an hour after the meal.; Other Names: FZHY; Drug: Vitamin C tablets; Vitamin C tablets, administration: 0.2g/time, 3 times/ day, oral； Other Names: VC; Other: respiratory function rehabilitation training; Health exercise, once a day
Placebo Comparator: Placebo Group; usual treatment (respiratory function rehabilitation training + Vitamin C tablets); placebo	Drug: Vitamin C tablets; Vitamin C tablets, administration: 0.2g/time, 3 times/ day, oral； Other Names: VC; Other: respiratory function rehabilitation training; Health exercise, once a day; Drug: Placebo; Placebo , administration: 0.4g/tablet, 1.6g/time, 3 times/day, oral; administered half an hour after the meal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The improvement proportion of pulmonary fibrosis	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.	Week 24
The improvement of lung function	FVC, FEV1, FVC/FEV1	Week 24

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: ShuGuang Hospital
• Collaborators: Hubei Hospital of Traditional Chinese Medicine; Wuhan No.1 Hospital; Wuhan Third Hospital; Jingmen No.1 People's Hospital; Huangshi Hospital of Traditional Chinese Medicine
• Investigators: Study Director: Chenghai Liu, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Actual): March 24, 2021
• Study Completion (Actual): March 24, 2021

Study Registration Dates

• First Submitted: February 15, 2020
• First Submitted That Met QC Criteria: February 19, 2020
• First Posted (Actual): February 21, 2020

Study Record Updates

• Last Update Posted (Actual): January 3, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Fibrosis; COVID-19; Pulmonary Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: Fzhy-ncp-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No