Common Cold
Conditions
Brief summary
The aim of this clinical trial is to investigate the effect of Iota-Carrageenan treatment on cold symptoms. The effect of treatment on the duration of the cold and the patients viral load plus cytokine level indicating the inflammatory response will be analyzed.
Interventions
DEVICEPlacebo
Nasal spray saline
DEVICEIota-Carrageenan
Nasal spray containing 1.20 g/l Iota-Carrageenan in saline
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Patients consider that they are in an early stage of common cold with symptoms of no more than 48 hours duration * Symptom score of equal or more than 1 for for at least one of the symptoms sore throat, runny nose and blocked nose on a 0-3 verbal rating scale * Total symptom score of equal or less 9 for symptoms headache, muscle ache, chilliness, sore throat, blocked nose, runny nose, cough, and sneezing measured on a 0-3 verbal rating scale * Patients agree to refrain from taking any products intended to prevent, intervene in, or treat cough/colds/flu, starting at study entry and continuing through day 10 (e.g. those containing zinc, Echinacea); use of a daily multivitamin is allowed.
Exclusion criteria
* Known hypersensitivity or are allergic to any component of the test device * Clinically significant cardiovascular, endocrinological, neurological, respiratory, gastrointestinal disease or history or any current disease that is considered by the investigator as a reason for exclusion e.g. current allergic rhinitis, chronic obstructive pulmonary disease * Severe nasal septum deviation or other condition that could cause nasal obstruction such as the presence of nasal polyps. * History of nasal or sinus surgery that in the opinion of the investigator may influence symptom scores * Taking any prescribed medication other than for contraception, that is considered by the investigator as a reason for exclusion e.g. systemic steroids, intranasal medicines, antibiotics * Common cold or flu like symptoms for more than 48 hours. * Recent (within the previous 2 days) intake of a common cold medicine that in the opinion of the investigator may influence symptom scores (analgesics, nasal decongestants, cough medicines) * Current smoker (more than 10 cigarettes a day)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Symptom Score (TSS) Over Days 2 to 4 (TSS2-4) | Days 2, 3 and 4 | The total symptom score (TSS) is the sum of the 8 single common cold symptom scores consisting of 3 systemic (headache, muscle ache and chilliness) and 5 local (sore throat, blocked nose, runny nose, cough and sneezing) symptoms. Each common cold symptom was scored on a 4-point ordinal scale: * 0 = symptom not present * 1 = mild symptom (I can feel it but it has not disturbed or irritated me) * 2 = moderate symptom (symptom has disturbed and irritated me some of the time) * 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean over days 2 to 4 (TSS2-4) was calculated as (TSS2 + TSS3 + TSS4)/3 where TSS2, TSS3 and TSS4 are the total symptom scores calculated for days 2, 3 and 4 respectively. TSS2-4 ranges from 0 (no symptoms) to 24 (severe symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean of the Sum of 3 Single Systemic Common Cold Symptom Scores Over Days 2 to 4 (SSS2-4) | Days 2, 3 and 4 | The mean of the sum of 3 single systemic common cold symptom scores (headache, muscle ache, chilliness). Each common cold symptom was scored on a 4-point ordinal scale: * 0 = symptom not present * 1 = mild symptom (I can feel it but it has not disturbed or irritated me) * 2 = moderate symptom (symptom has disturbed and irritated me some of the time) * 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean of the sum of 3 single systemic common cold symptom scores over days 2-4 was calculated as (SSS2 + SSS3 + SSS4)/3 where SSS2, SSS3 and SSS4 are the systemic common cold symptom scores calculated for days 2, 3 and 4 respectively. SSS2-4 ranges from 0 (no symptoms) to 9 (severe symptoms). |
| Mean of the Sum of 5 Single Local Common Cold Symptom Scores Mean Over Days 2 to 4 (LSS2-4) | Days 2, 3 and 4 | The mean of the sum of 5 single local common cold symptom scores (sore throat, blocked nose, runny nose, cough and sneezing). Each common cold symptom was scored on a 4-point ordinal scale: * 0 = symptom not present * 1 = mild symptom (I can feel it but it has not disturbed or irritated me) * 2 = moderate symptom (symptom has disturbed and irritated me some of the time) * 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean of the sum of 5 single local common cold symptom scores over days 2 to 4 was calculated as (LSS2 + LSS3 + LSS4)/3 where LSS2, LSS3 and LSS4 are the local common cold symptom scores calculated for days 2, 3 and 4 respectively. LSS2-4 ranges from 0 (no symptoms) to 15 (severe symptoms). |
| Area Under the Curve (AUC) Over the 10-day Period for the TSS (AUC-TSS 1-10) | Days 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 | The total symptom score (TSS) is the sum of the 8 single common cold symptom scores consisting of 3 systemic (headache, muscle ache and chilliness) and 5 local (sore throat, blocked nose, runny nose, cough and sneezing) symptoms. Each common cold symptom was scored on a 4-point ordinal scale: * 0 = symptom not present * 1 = mild symptom (I can feel it but it has not disturbed or irritated me) * 2 = moderate symptom (symptom has disturbed and irritated me some of the time) * 3 = severe symptom (symptom has disturbed and irritated me most of the time) The Area under the curve (AUC) over the 10-day period for the total symptom score (AUC-TSS 1-10) was calculated as the sum of the TSS calculated on each day from day 1 to day 10. AUC-TSS 1-10 ranges from 0 (no symptoms) to 270 (severe symptoms). |
| Duration of the Cold | Baseline up to 10 days | Duration of the common cold was assessed by the question Do you still have a cold? at the end of each treatment day. The duration of the cold was defined as ended by the first day of a No answer to this daily question. |
| Patient Overall Assessment of Efficacy | Day 10 | Patient overall assessment of efficacy was assessed by the question How effective was the treatment in relieving your common cold symptoms? at day 10. A 5-point scale was used (0=poor, 1=fair, 2=good, 3=very good, 4=excellent). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril. | 100 |
| Bisolviral Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril. | 100 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Bisolviral | Total |
|---|---|---|---|
| Age, Continuous | 19.93 years STANDARD_DEVIATION 1.9 | 20.01 years STANDARD_DEVIATION 2.37 | 19.97 years STANDARD_DEVIATION 2.14 |
| Sex: Female, Male Female | 62 Participants | 60 Participants | 122 Participants |
| Sex: Female, Male Male | 38 Participants | 40 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 100 | 0 / 100 |
| serious Total, serious adverse events | 0 / 100 | 0 / 100 |
Outcome results
Primary
Total Symptom Score (TSS) Over Days 2 to 4 (TSS2-4)
The total symptom score (TSS) is the sum of the 8 single common cold symptom scores consisting of 3 systemic (headache, muscle ache and chilliness) and 5 local (sore throat, blocked nose, runny nose, cough and sneezing) symptoms. Each common cold symptom was scored on a 4-point ordinal scale: * 0 = symptom not present * 1 = mild symptom (I can feel it but it has not disturbed or irritated me) * 2 = moderate symptom (symptom has disturbed and irritated me some of the time) * 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean over days 2 to 4 (TSS2-4) was calculated as (TSS2 + TSS3 + TSS4)/3 where TSS2, TSS3 and TSS4 are the total symptom scores calculated for days 2, 3 and 4 respectively. TSS2-4 ranges from 0 (no symptoms) to 24 (severe symptoms).
Time frame: Days 2, 3 and 4
Population: Full analysis set (FAS) which included all randomised patients who used at least one dose of trial treatment, who provided a baseline total symptom score (TSS) as well as any post-treatment data for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Symptom Score (TSS) Over Days 2 to 4 (TSS2-4) | 6.390 units on a scale | Standard Error 0.254 |
| Bisolviral | Total Symptom Score (TSS) Over Days 2 to 4 (TSS2-4) | 5.777 units on a scale | Standard Error 0.253 |
p-value: 0.089595% CI: [-1.321, 0.095]ANCOVA
Secondary
Area Under the Curve (AUC) Over the 10-day Period for the TSS (AUC-TSS 1-10)
The total symptom score (TSS) is the sum of the 8 single common cold symptom scores consisting of 3 systemic (headache, muscle ache and chilliness) and 5 local (sore throat, blocked nose, runny nose, cough and sneezing) symptoms. Each common cold symptom was scored on a 4-point ordinal scale: * 0 = symptom not present * 1 = mild symptom (I can feel it but it has not disturbed or irritated me) * 2 = moderate symptom (symptom has disturbed and irritated me some of the time) * 3 = severe symptom (symptom has disturbed and irritated me most of the time) The Area under the curve (AUC) over the 10-day period for the total symptom score (AUC-TSS 1-10) was calculated as the sum of the TSS calculated on each day from day 1 to day 10. AUC-TSS 1-10 ranges from 0 (no symptoms) to 270 (severe symptoms).
Time frame: Days 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve (AUC) Over the 10-day Period for the TSS (AUC-TSS 1-10) | 41.214 units on a scale * days | Standard Error 2.199 |
| Bisolviral | Area Under the Curve (AUC) Over the 10-day Period for the TSS (AUC-TSS 1-10) | 41.941 units on a scale * days | Standard Error 2.187 |
p-value: 0.814895% CI: [-5.39, 6.845]ANCOVA
Secondary
Duration of the Cold
Duration of the common cold was assessed by the question Do you still have a cold? at the end of each treatment day. The duration of the cold was defined as ended by the first day of a No answer to this daily question.
Time frame: Baseline up to 10 days
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of the Cold | 7 days |
| Bisolviral | Duration of the Cold | 8 days |
p-value: 0.1887Log Rank
Secondary
Mean of the Sum of 3 Single Systemic Common Cold Symptom Scores Over Days 2 to 4 (SSS2-4)
The mean of the sum of 3 single systemic common cold symptom scores (headache, muscle ache, chilliness). Each common cold symptom was scored on a 4-point ordinal scale: * 0 = symptom not present * 1 = mild symptom (I can feel it but it has not disturbed or irritated me) * 2 = moderate symptom (symptom has disturbed and irritated me some of the time) * 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean of the sum of 3 single systemic common cold symptom scores over days 2-4 was calculated as (SSS2 + SSS3 + SSS4)/3 where SSS2, SSS3 and SSS4 are the systemic common cold symptom scores calculated for days 2, 3 and 4 respectively. SSS2-4 ranges from 0 (no symptoms) to 9 (severe symptoms).
Time frame: Days 2, 3 and 4
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean of the Sum of 3 Single Systemic Common Cold Symptom Scores Over Days 2 to 4 (SSS2-4) | 1.297 units on a scale | Standard Error 0.103 |
| Bisolviral | Mean of the Sum of 3 Single Systemic Common Cold Symptom Scores Over Days 2 to 4 (SSS2-4) | 1.121 units on a scale | Standard Error 0.103 |
p-value: 0.23195% CI: [-0.464, 0.113]ANCOVA
Secondary
Mean of the Sum of 5 Single Local Common Cold Symptom Scores Mean Over Days 2 to 4 (LSS2-4)
The mean of the sum of 5 single local common cold symptom scores (sore throat, blocked nose, runny nose, cough and sneezing). Each common cold symptom was scored on a 4-point ordinal scale: * 0 = symptom not present * 1 = mild symptom (I can feel it but it has not disturbed or irritated me) * 2 = moderate symptom (symptom has disturbed and irritated me some of the time) * 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean of the sum of 5 single local common cold symptom scores over days 2 to 4 was calculated as (LSS2 + LSS3 + LSS4)/3 where LSS2, LSS3 and LSS4 are the local common cold symptom scores calculated for days 2, 3 and 4 respectively. LSS2-4 ranges from 0 (no symptoms) to 15 (severe symptoms).
Time frame: Days 2, 3 and 4
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean of the Sum of 5 Single Local Common Cold Symptom Scores Mean Over Days 2 to 4 (LSS2-4) | 5.100 units on a scale | Standard Error 0.215 |
| Bisolviral | Mean of the Sum of 5 Single Local Common Cold Symptom Scores Mean Over Days 2 to 4 (LSS2-4) | 4.657 units on a scale | Standard Error 0.214 |
p-value: 0.146595% CI: [-1.042, 0.156]ANCOVA
Secondary
Patient Overall Assessment of Efficacy
Patient overall assessment of efficacy was assessed by the question How effective was the treatment in relieving your common cold symptoms? at day 10. A 5-point scale was used (0=poor, 1=fair, 2=good, 3=very good, 4=excellent).
Time frame: Day 10
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient Overall Assessment of Efficacy | Very good | 11.3 percentage of participants |
| Placebo | Patient Overall Assessment of Efficacy | Fair | 33.0 percentage of participants |
| Placebo | Patient Overall Assessment of Efficacy | Good | 36.1 percentage of participants |
| Placebo | Patient Overall Assessment of Efficacy | Poor | 17.5 percentage of participants |
| Placebo | Patient Overall Assessment of Efficacy | Excellent | 2.1 percentage of participants |
| Bisolviral | Patient Overall Assessment of Efficacy | Poor | 19.4 percentage of participants |
| Bisolviral | Patient Overall Assessment of Efficacy | Excellent | 2.0 percentage of participants |
| Bisolviral | Patient Overall Assessment of Efficacy | Very good | 16.3 percentage of participants |
| Bisolviral | Patient Overall Assessment of Efficacy | Good | 33.7 percentage of participants |
| Bisolviral | Patient Overall Assessment of Efficacy | Fair | 28.6 percentage of participants |
p-value: 0.695495% CI: [0.666, 1.84]Regression, Logistic