Evaluating the Efficacy and Safety of Bromhexine Hydrochloride Tablets Combined With Standard Treatment/ Standard Treatment in Patients With Suspected and Mild Novel Coronavirus Pneumonia (COVID-19)

• ClinicalTrials.gov Identifier: NCT04273763
• Recruitment Status: Active, not recruiting
• First Posted: February 18, 2020
• Last Update Posted: May 1, 2020
• Sponsor: Second Affiliated Hospital of Wenzhou Medical University
• Collaborator: Wanbangde Pharmaceutical Group Co., LTD
• Information provided by (Responsible Party): Second Affiliated Hospital of Wenzhou Medical University

Study Description

Brief Summary:

Compare the efficacy and safety of Bromhexine Hydrochloride Tablets combined with standard treatment/ standard treatment in patients with suspected and mild, or common novel coronavirus pneumonia (COVID-19).

Random, open, group sequential design.

Condition or disease	Intervention/treatment	Phase
Novel Coronavirus Pneumonia; 2019-nCoV	Drug: Bromhexine Hydrochloride Tablets; Drug: Arbidol Hydrochloride Granules; Drug: Recombinant Human Interferon α2b Spray	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluating the Efficacy and Safety of Bromhexine Hydrochloride Tablets Combined With Standard Treatment/ Standard Treatment in Patients With Suspected and Mild Novel Coronavirus Pneumonia (COVID-19)
• Actual Study Start Date: February 16, 2020
• Estimated Primary Completion Date: May 10, 2020
• Estimated Study Completion Date: June 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A; Treatment group	Drug: Bromhexine Hydrochloride Tablets; Bromhexine Hydrochloride Tablets; Drug: Arbidol Hydrochloride Granules; Standard treatment refers to the latest edition of Pneumonia Diagnosis and Treatment Scheme for Novel Coronavirus Infection. Arbidol Hydrochloride Granules is recommended but not enforced to use.; Drug: Recombinant Human Interferon α2b Spray; Standard treatment refers to the latest edition of Pneumonia Diagnosis and Treatment Scheme for Novel Coronavirus Infection.
Active Comparator: Group B; Control group	Drug: Arbidol Hydrochloride Granules; Standard treatment refers to the latest edition of Pneumonia Diagnosis and Treatment Scheme for Novel Coronavirus Infection. Arbidol Hydrochloride Granules is recommended but not enforced to use.; Drug: Recombinant Human Interferon α2b Spray; Standard treatment refers to the latest edition of Pneumonia Diagnosis and Treatment Scheme for Novel Coronavirus Infection.

Outcome Measures

Primary Outcome Measures :

1. Time to clinical recovery after treatment [ Time Frame: within 14 days from the start of medication ]
   Defined as random to fever, respiratory rate return to normal and cough remission over 48 hours.
2. Rate of aggravation [ Time Frame: within 14 days from the start of medication ]
   Aggravation was defined as(one of them): respiratory distress, RR ≥ 30 times / min; SpO2 ≤ 93% in resting state; arterial partial pressure of oxygen (PaO2) /concentration of oxygen (FiO2) ≤ 300mmHg

Secondary Outcome Measures :

1. Clinical remission rate [ Time Frame: within 14 days from the start of medication ]
   Clinical remission was defined as (one of them): sustained (more than 48 hours) alleviation of illness based on symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) all being absent and no evidence for progression.
2. Dynamic changes of oxygenation index [ Time Frame: within 14 days from the start of medication ]
   oxygenation index
3. Time to cure [ Time Frame: within 14 days from the start of medication ]
   time of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery
4. rate to cure [ Time Frame: within 14 days from the start of medication ]
   proportion of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery among infected patients
5. Time to defervescence [ Time Frame: within 14 days from the start of medication ]
   defervescence is defined as below 37 Celcius degrees（ear temperature）
6. Time to cough remission [ Time Frame: within 14 days from the start of medication ]
7. Time to dyspnea remission [ Time Frame: within 14 days from the start of medication ]
8. Days of supplemental oxygenation [ Time Frame: within 14 days from the start of medication ]
9. Rate of patients with requring supplemental oxygen [ Time Frame: within 14 days from the start of medication ]
10. Rate of patients with mechanical ventilation [ Time Frame: within 14 days from the start of medication ]
11. Time of negative COVID-19 nucleic acid results [ Time Frame: within 14 days from the start of medication ]
12. Rate of negative COVID-19 nucleic acid results [ Time Frame: within 14 days from the start of medication ]
13. Rate of ICU admission [ Time Frame: within 14 days from the start of medication ]
14. 28-day mortality [ Time Frame: From the first day of screening to the day of follow-up (28 days) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Aged between 18 and 80 years (Including 18and 80years, male or female).

• One of them:

  1. Laboratory (RT-PCR) and clinical symptoms confirmed case of novel coronavirus pneumonia (COVID-19).
  2. Patients diagnosed clinically as suspected cases.
• Ability to communicate well with researchers and sign the informed consent Form (ICF) voluntarily.

Exclusion Criteria:

• ALT≥5 times of ULN, level of total bilirubin≥3 times of ULN, or Cr≥1.5 times of ULN.
• Patients with serious severe liver disease.
• Excluded who diagnosed as pneumonia patients with novel coronavirus infection of severe type and critical type. 【Diagnostic criteria reference the official guideline "Pneumonia Diagnosis and Treatment Scheme for Novel Coronavirus Infection (Trial Version 5) "】.
• Patients with previous history of severe gastrointestinal diseases such as gastric ulcers and bleeding.
• Patients with lactose intolerance.
• Patients who are allergic to the components of this medicine (Major components: Bromhexine Hydrochloride; excipient: starch, lactose, magnesium stearate).
• Positive serum pregnancy test result for women with childbearing potential at screening or lactating women.
• Other circumstances that the researcher considers inappropriate to participate in this study.

Contacts and Locations

Locations

China, Zhejiang

The Second AffIliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China, 325000

Sponsors and Collaborators

Second Affiliated Hospital of Wenzhou Medical University

Wanbangde Pharmaceutical Group Co., LTD

Investigators

• Study Chair: XIAN SHEN, phd; The 2nd Affiliated Hospital of Wenzhou Medical University

More Information

• Responsible Party: Second Affiliated Hospital of Wenzhou Medical University
• ClinicalTrials.gov Identifier: NCT04273763
• Other Study ID Numbers: 2019NCP1.0
• First Posted: February 18, 2020
• Last Update Posted: May 1, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Coronavirus Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Interferons; Bromhexine; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Expectorants; Respiratory System Agents