Banlangen Granules Anti-seasonal Influenza Study (BLG)

Banlangen Granules Anti-seasonal Influenza Study: a Randomized, Double Blind, Positive and Placebo Controlled，Clinical Study.

This study aimed to evaluate the efficacy and safety of the nature herbal medicine Banlangen granules in patients infected with seasonal influenza A (H1N1,H3N2) and influenza B virus.

Study Overview

• Status: Unknown
• Conditions: Influenza
• Intervention / Treatment: Drug: placebo of oseltamivir phosphate; Drug: placebo of Banlangen(Radix Isatidis) granules; Drug: Banlangen (Radix Isatidis) granules; Drug: oseltamivir phosphate

Detailed Description

Inclusion criteria:

1. Patients have confirmed influenza A(H1N1,H3N2) or influenza B virus infection by real time PCR
2. age between 18-65 years old
3. axillary temperature ≥38ºC and with at least two constitutional symptoms (headache, chill, myalgia ，or fatigue) and one respiratory symptom (cough ，sore throat,or coryza) .
4. Illness onset had to be within 36 hours, and informed consent was obtained.

Exclusion criteria:

1. age younger than 18 or older than 65 years old.
2. patients confirmed with bronchitis, pneumonia,pleural effusion and interstitial lung disease by Chest imaging (chest X-ray or CT) .
3. Blood routine screening tests shows numeration of leukocyte 10.0×109/L or Neutrophil percentage ≥80%.
4. Those have got suppurative tonsillitis or cough purulent sputum.
5. Those with underling primary disorders, such as hematological disease, chronic obstructive pulmonary disease（FEV1/FVC<70％，FEV1/ predicated value<50％； or respiratory failure or right heart failure）， hepatic disease（ALT or AST≥triple ULN）, renal disease（Serum Creatinine>2mg/dL）,chronic congestive heart failure( NYHA Ⅲ-IV)

7. Patient is allergic to the study medication(s). 8. Women who are pregnant or may possibly become pregnant or are lactating with a positive urine pregnant test, obesity (abody mass index (BMI) of 25 kg/m2 or more).

9. Those with immunodeficiency ,such as malignant tumor ; Organs or bone marrow transplantation ; AIDS ;or taking immune inhibitors during the last 3 months.

10. Doubt or does alcohol/drug abuse of history. 11. Those have participated in other clinical trial within three month before study randomization.

12. Two weeks before the test , those with acute respiratory Infection，otitis,or nasosinusitis .

13. Those already vaccinated or who will receive influenza vaccine. 14. other reasons not suitable for enrollment based on the investigator's discretion.

The primary efficacy endpoint:

1. The primary end point was the duration of illness which was defined as the time from onset of symptoms to the alleviation of the ten influenza-like symptoms including , nasal obstruction, running nose, cough, sore throat, headache, fatigue, myalgia, chills and sweating.
2. The time to defervescence, defined as the time from the first dose of study medication to the time when the body temperature declined to lower than 37.4ºC and was sustained for at least 24 hours.

Secondary efficacy endpoint:

The secondary end points included: 1) viral shedding duration, defined as the time from the illness onset to the first time the viral nucleic acid test was negative; 2) the severity of the disease,assessed by an area under the curve (AUC) analysis of a total of nine influenza-like symptom scores, the AUC was calculated as the product of the daily symptom scores times the duration of illness;3)frequency of Usage of Acetaminophen;4)and incidence of secondary complications of influenza, such as otitis, bronchitis, pneumonia，Nasosinusitis ,suppurative tonsillitis,acute parotitis，Reye'ssyndrome，central nervous system disease, Myocarditis and pericarditis, acute myositis, and toxic shock syndrome.5) economic evaluation.

Specimen:

the pharyngeal or the throat swab，blood. Pharyngea /throat secretions will be obtained from the upper respiratory tract of each patient.

All specimens will be stored at -80℃ in virus laboratory of the first affiliated hospital of guangzhou medical university for 5 years.

• Study Type: Interventional
• Enrollment (Anticipated): 177
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yuedong Cai, Master; Phone Number: 86-20-66282326; Email: caiyuedong@813zy.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510230
      • Recruiting
      • Guangzhou Institute of Respiratory Disease
      • Contact: Nan S Zhong, PHD; Phone Number: 020-83062718; Email: nanshan@vip.163.com
      • Principal Investigator: N S Zhong, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

with confirmed influenza A(H1N1,H3N2) or influenza B virus infection by real time RT-PCR (rRT-PCR), age between 18-65 years old, axillary temperature ≥38ºC and with at least two constitutional symptoms (headache, chill, myalgia ，or fatigue) and one respiratory symptom (cough ，sore throat,or coryza) . Illness onset had to be within 36 hours, and informed consent was obtained.

Exclusion Criteria:

1. age younger than 18 or older than 65 years old.
2. patients confirmed with bronchitis, pneumonia,pleural effusion and interstitial lung disease by Chest imaging (chest X-ray or CT) .
3. Blood routine screening tests shows numeration of leukocyte 10.0×109/L or Neutrophil percentage ≥80%.
4. Those have got suppurative tonsillitis or cough purulent sputum.
5. Those with underling primary disorders, such as hematological disease, chronic obstructive pulmonary disease（FEV1/FVC<70％，FEV1/ predicated value<50％； or respiratory failure or right heart failure）， hepatic disease（ALT or AST≥triple ULN）, renal disease（Serum Creatinine>2mg/dL）,chronic congestive heart failure( NYHA Ⅲ-IV)

7. Patient is allergic to the study medication(s). 8. Women who are pregnant or may possibly become pregnant or are lactating with a positive urine pregnant test, obesity (abody mass index (BMI) of 25 kg/m2 or more).

9. Those with immunodeficiency ,such as malignant tumor ; Organs or bone marrow transplantation ; AIDS ;or taking immune inhibitors during the last 3 months.

10. Doubt or does alcohol/drug abuse of history. 11. Those have participated in other clinical trial within three month before study randomization.

12. Two weeks before the test , those with acute respiratory Infection，otitis,or nasosinusitis .

13. Those already vaccinated or who will receive influenza vaccine. 14.other reasons not suitable for enrollment based on the investigator's discretion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; placebo of oseltamivir phosphate and placebo of Banlangen(Radix Isatidis) granules.	Drug: placebo of oseltamivir phosphate; Drug: placebo of Banlangen(Radix Isatidis) granules
Experimental: Banlangen granules & placebo; Banlangen(Radix Isatidis) granules and placebo of oseltamivir phosphate	Drug: placebo of oseltamivir phosphate; Drug: Banlangen (Radix Isatidis) granules
Active Comparator: oseltamivir phosphate & placebo; oseltamivir phosphate and placebo of Banlangen(Radix Isatidis) granules	Drug: placebo of Banlangen(Radix Isatidis) granules; Drug: oseltamivir phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improving the flu-like symptoms, such as fever etc	The primary end point was the duration of illness which was defined as the time from onset of symptoms to the alleviation of the ten influenza-like symptoms including , nasal obstruction, running nose, cough, sore throat, headache, fatigue, myalgia, chills and sweating.	21+7days
Improving the flu-like symptoms, such as fever etc	The time to defervescence, defined as the time from the first dose of study medication to the time when the body temperature declined to lower than 37.4ºC and was sustained for at least 24 hours.	21+7days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
others	viral shedding duration, defined as the time from the illness onset to the first time the viral nucleic acid test was negative	21+7days
Others	the severity of the disease,assessed by an area under the curve (AUC) analysis of a total of nine influenza-like symptom scores, the AUC was calculated as the product of the daily symptom scores times the duration of illness	21+7days
Others	frequency of Usage of Acetaminophen	21+7days
Others	incidence of secondary complications of influenza	21+7days
Others	economic evaluation	21+7days

Collaborators and Investigators

• Sponsor: Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
• Collaborators: Guangzhou Institute of Respiratory Disease
• Investigators: Study Chair: Nanshan Zhong, PhD, Guangzhou Institute of Respiratory Disease

Publications and helpful links

General Publications

• Li ZT, Li L, Chen TT, Li CY, Wang DQ, Yang ZF, Zhong NS. Efficacy and safety of Ban-Lan-Gen granules in the treatment of seasonal influenza: study protocol for a randomized controlled trial. Trials. 2015 Mar 28;16:126. doi: 10.1186/s13063-015-0645-x.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): November 1, 2016

Study Registration Dates

• First Submitted: November 18, 2012
• First Submitted That Met QC Criteria: September 3, 2014
• First Posted (Estimate): September 5, 2014

Study Record Updates

• Last Update Posted (Estimate): March 4, 2016
• Last Update Submitted That Met QC Criteria: March 2, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: influenza A (H1N1,H3N2); influenza B virus
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: HWBY-001