Efficacy and Safety of a Herbal Medicinal Product (Dry Extract BNO 1016) in Patients With Acute Rhinosinusitis

• Sponsor: Bionorica SE (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01146860
• Collaborator: (none)
• Enrollment: 386
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 130.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the dry extract BNO 1016 is effective and safe in the treatment of acute rhinosinusitis in adults.

Condition or Disease	Intervention/Treatment	Phase
Acute Rhinosinusitis	Drug: BNO 1016; Drug: Placebo	Phase 3

Detailed Description

The aim of this clinical study is to investigate the efficacy of a 15-days treatment with the herbal medicinal product BNO 1016 for therapy of acute rhinosinusitis in adult patients. Due to the considerable morbidity and the diminished quality of life experienced by people afflicted with acute rhinosinusitis an important aim of the treatment is to reduce the severity of rhinosinusitis symptoms and the duration of the disease. By grading the severity of the disease on the basis of the 5 main rhinosinusitis symptoms the investigator will assess the efficacy of the treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 386 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-centre, Double-blind, Placebo-controlled, Randomised, Parallel Group Study to Assess the Efficacy and Safety of a Herbal Medicinal Product (Dry Extract BNO 1016) in Patients With Acute Rhinosinusitis
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BNO 1016 sugar coated tablets with dry extract (80 mg) of 5 herbal drugs; dosage: 480 mg per day (2 tablets t.i.d.) duration: 15 days	Drug: BNO 1016; sugar coated tablets with dry extract (80 mg) of 5 herbal drugs; dosage: 480 mg per day (2 tablets t.i.d.) duration: 15 days; Other Names: Sinupret extract
Placebo Comparator: Placebo sugar coated tablets with identical appearance to active treatment; frequency: 2 tablets t.i.d. duration: 15 days	Drug: Placebo; sugar coated tablets with identical appearance to active treatment; frequency: 2 tablets t.i.d. duration 15 days; Other Names: Placebo to BNO 1016

Outcome Measures

Primary Outcome Measures

1. Major Symptom Score (MSS) Assessed by the Investigator [14 days]

   MSS: sum of the 5 main rhinosinusitis symptoms which are: rhinorrhea (anterior discharge), postnasal drip, nasal congestion, headache, facial pain/pressure. Each symptom is individually evaluated using the following 4-point rating scale (scoring system): 0 = none/not present, 1 = mild, 2 = moderate, 3 = severe. Thus the MSS ranges from a minimum of 0 to a maximum of 15 score points.

Secondary Outcome Measures

1. SNOT 20 Symptom Scores [14 days]

   Sino-Nasal Outcome Test (SNOT 20): 20 item questionnaire to assess the symptoms and emotional and social consequences of rhinosinusitis. The symptoms are assessed by the patient using a 6-point rating scale: 0 = not present / no problem, 1 = very mild problem, 2 = mild or slight problem, 3 = moderate problem, 4 = severe problem, 5 = problem as "bad as it can be". range: 0 to 100

2. Major Symptom Score Assessed by the Patient [14 days]

   MSS: sum of the 5 main rhinosinusitis symptoms which are: rhinorrhea (anterior discharge), postnasal drip, nasal congestion, headache, facial pain/pressure. Each symptom is individually evaluated using the following 4-point rating scale (scoring system): 0 = none/not present, 1 = mild, 2 = moderate, 3 = severe. Thus the MSS ranges from a minimum of 0 to a maximum of 15 score points.

3. Percentage of Patients Classified as Responders by the Investigator on a 4-point Rating Scale [14 days]

   General assessment of efficacy using a 4-point rating scale (symptoms healed, improved, unchanged, deteriorated). Patients whose symptoms are improved or healed will be classified as "responders" to treatment. Patients whose symptoms are unchanged or deteriorated as classified as "non-responders".

4. Ultrasonography of Paranasal Sinuses [14 days]

   Percentage of patients with signs of acute rhinosinusitis in ultrasonography of paranasal sinuses will be evaluated. Ultrasonography scans will be visually evaluated by the investigator for signs of rhinosinusitis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Diagnosis of acute rhinosinusitis

• characterized by a major symptom score (MSS) ≥ 8 and ≤ 12 points (minimum 0, maximum 15 points)

• individual score for facial pain/pressure ≥ 1 (mild) and ≤ 2 (moderate)

• confirmed by ultrasonography of paranasal sinuses

• with presence of symptoms ≤ 3 days prior to inclusion

Exclusion Criteria:

• Chronic rhinosinusitis

• Polyposis nasi

• Anatomical deviations of the nasal septum that significantly impair nasal and paranasal ventilation/airflow

• Acute symptoms of a known allergic rhinitis

• Patients with asthma who have a history of exacerbations within 30 days prior to study inclusion

• Signs or symptoms of fulminant bacterial sinusitis

• Odontogenic sinusitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dr. Rainer Jund, Specialist in Otorhinolaryngology	Puchheim		Germany	82178

Sponsors and Collaborators

• Bionorica SE

Investigators

• Study Chair: Rainer Jund, MD, Specialist in Otorhinolaryngology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bionorica SE
• ClinicalTrials.gov Identifier: NCT01146860
• Other Study ID Numbers: ARhiSi-2; 2009-016682-28
• First Posted: Jun 22, 2010
• Last Update Posted: Aug 2, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Bionorica SE: BNO 1016, acute rhinosinusitis
• Additional relevant MeSH terms: Sinusitis

Study Results

Participant Flow

Recruitment Details	January 2010 to April 2010 37 centres (16 ENT and 21 specialists in internal medicine and general practitioners

Arm/Group Title	BNO 1016	Placebo
Arm/Group Description	sugar coated tablets with dry extract (80 mg) of 5 herbal drugs; daily dose: 480 mg (2 tablets tid)	sugar coated tablets of identical appearance to active treatment
Period Title: Overall Study
STARTED	194	192
COMPLETED	194	191
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	BNO 1016	Placebo	Total
Arm/Group Description	sugar coated tablets	sugar coated tablets	Total of all reporting groups
Overall Participants	194	192	386
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	174 89.7%	182 94.8%	356 92.2%
>=65 years	20 10.3%	10 5.2%	30 7.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.0 (15.4)	40.4 (14.3)	40.7 (14.9)
Sex: Female, Male (Count of Participants)
Female	127 65.5%	122 63.5%	249 64.5%
Male	67 34.5%	70 36.5%	137 35.5%
Region of Enrollment (participants) [Number]
Germany	194 100%	192 100%	386 100%

Outcome Measures

1. Primary Outcome

Title	Major Symptom Score (MSS) Assessed by the Investigator
Description	MSS: sum of the 5 main rhinosinusitis symptoms which are: rhinorrhea (anterior discharge), postnasal drip, nasal congestion, headache, facial pain/pressure. Each symptom is individually evaluated using the following 4-point rating scale (scoring system): 0 = none/not present, 1 = mild, 2 = moderate, 3 = severe. Thus the MSS ranges from a minimum of 0 to a maximum of 15 score points.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

FAS: randomised patients with at least one documented application of the drug and post-baseline efficacy data

Arm/Group Title	BNO 1016	Placebo
Arm/Group Description	sugar coated tablets	sugar coated tablets
Measure Participants	190	190
Mean (Standard Error) [units on a scale]	2.38 (0.18)	3.41 (0.24)

2. Secondary Outcome

Title	SNOT 20 Symptom Scores
Description	Sino-Nasal Outcome Test (SNOT 20): 20 item questionnaire to assess the symptoms and emotional and social consequences of rhinosinusitis. The symptoms are assessed by the patient using a 6-point rating scale: 0 = not present / no problem, 1 = very mild problem, 2 = mild or slight problem, 3 = moderate problem, 4 = severe problem, 5 = problem as "bad as it can be". range: 0 to 100
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

FAS: randomised patients with at least one documented application of the drug and post-baseline efficacy data

Arm/Group Title	BNO 1016	Placebo
Arm/Group Description	sugar coated tablets	sugar coated tablets
Measure Participants	190	190
Mean (Standard Deviation) [units on a scale (range: 0 - 100)]	11.02 (12.72)	15.76 (16.26)

3. Secondary Outcome

Title	Major Symptom Score Assessed by the Patient
Description	MSS: sum of the 5 main rhinosinusitis symptoms which are: rhinorrhea (anterior discharge), postnasal drip, nasal congestion, headache, facial pain/pressure. Each symptom is individually evaluated using the following 4-point rating scale (scoring system): 0 = none/not present, 1 = mild, 2 = moderate, 3 = severe. Thus the MSS ranges from a minimum of 0 to a maximum of 15 score points.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

FAS: randomised patients with at least one documented application of the drug and post-baseline efficacy data

Arm/Group Title	BNO 1016	Placebo
Arm/Group Description	sugar coated tablets	sugar coated tablets
Measure Participants	190	190
Mean (Standard Error) [units on a scale]	2.62 (0.21)	3.48 (0.24)

4. Secondary Outcome

Title	Percentage of Patients Classified as Responders by the Investigator on a 4-point Rating Scale
Description	General assessment of efficacy using a 4-point rating scale (symptoms healed, improved, unchanged, deteriorated). Patients whose symptoms are improved or healed will be classified as "responders" to treatment. Patients whose symptoms are unchanged or deteriorated as classified as "non-responders".
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

FAS: randomised patients with at least one documented application of the drug and post-baseline efficacy data

Arm/Group Title	BNO 1016	Placebo
Arm/Group Description	sugar coated tablets	sugar coated tablets
Measure Participants	190	190
Number [percentage of patients]	94.2	87.4

5. Secondary Outcome

Title	Ultrasonography of Paranasal Sinuses
Description	Percentage of patients with signs of acute rhinosinusitis in ultrasonography of paranasal sinuses will be evaluated. Ultrasonography scans will be visually evaluated by the investigator for signs of rhinosinusitis.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

FAS: randomised patients with at least one documented application of the drug and post-baseline efficacy data

Arm/Group Title	BNO 1016	Placebo
Arm/Group Description	sugar coated tablets	sugar coated tablets
Measure Participants	190	190
Number [percentage of patients]	26.8	38.4

Adverse Events

Arm/Group Title	BNO 1016		Placebo
Arm/Group Description	sugar coated tablets		sugar coated tablets
All Cause Mortality
	BNO 1016		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	BNO 1016		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/194 (0%)		0/191 (0%)
Other (Not Including Serious) Adverse Events
	BNO 1016		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/194 (9.8%)		27/191 (14.1%)
Cardiac disorders
Palpitations	0/194 (0%)	0	1/191 (0.5%)	1
Ear and labyrinth disorders
Cerumen impaction	2/194 (1%)	2	0/191 (0%)	0
Ear pain	1/194 (0.5%)	1	0/191 (0%)	0
Tinnitus	1/194 (0.5%)	1	0/191 (0%)	0
Eye disorders
Eye discharge	0/194 (0%)	0	1/191 (0.5%)	2
Gastrointestinal disorders
Abdominal discomfort	0/194 (0%)	0	1/191 (0.5%)	1
Abdominal upper pain	0/194 (0%)	0	1/191 (0.5%)	1
Diarrhoea	2/194 (1%)	2	3/191 (1.6%)	3
Flatulence	1/194 (0.5%)	1	0/191 (0%)	0
Nausea	1/194 (0.5%)	1	0/191 (0%)	0
Toothache	0/194 (0%)	0	3/191 (1.6%)	3
General disorders
Facial pain	0/194 (0%)	0	1/191 (0.5%)	1
Hepatobiliary disorders
Cholelithiasis	0/194 (0%)	0	1/191 (0.5%)	1
Immune system disorders
Hypersensitivity	0/194 (0%)	0	2/191 (1%)	2
Infections and infestations
Bronchitis	0/194 (0%)	0	1/191 (0.5%)	1
Furuncle	1/194 (0.5%)	1	0/191 (0%)	0
Gastroenteritis	3/194 (1.5%)	3	2/191 (1%)	2
Laryngitis	1/194 (0.5%)	1	0/191 (0%)	0
Viral infection	0/194 (0%)	0	1/191 (0.5%)	1
Injury, poisoning and procedural complications
Contusion	0/194 (0%)	0	1/191 (0.5%)	1
Injury	1/194 (0.5%)	1	1/191 (0.5%)	1
Investigations
ASAT increased	0/194 (0%)	0	1/191 (0.5%)	1
Musculoskeletal and connective tissue disorders
Arthropathy	1/194 (0.5%)	1	0/191 (0%)	0
Back pain	1/194 (0.5%)	1	2/191 (1%)	2
Nervous system disorders
Dizziness	2/194 (1%)	2	1/191 (0.5%)	1
Psychiatric disorders
Depressed mood	1/194 (0.5%)	1	1/191 (0.5%)	1
Reproductive system and breast disorders
Genital discharge	0/194 (0%)	0	1/191 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/194 (0%)	0	1/191 (0.5%)	1
Epistaxis	0/194 (0%)	0	1/191 (0.5%)	1
Nasal discomfort	0/194 (0%)	0	1/191 (0.5%)	1
Oropharyngeal pain	0/194 (0%)	0	1/191 (0.5%)	1
Skin and subcutaneous tissue disorders
Ingrown hair	0/194 (0%)	0	1/191 (0.5%)	1
Pruritus	1/194 (0.5%)	1	0/191 (0%)	0
Surgical and medical procedures
Surgery	1/194 (0.5%)	1	0/191 (0%)	0

Limitations/Caveats

Headache and facial pain are rated by investigator based on the description of the patient. This was done to ensure a uniform rating of symptom severity across the investigational sites but nevertheless subjective and open to error.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.