Clinical trial NCT04073251: Efficacy, Safety and Palatability of the Syrup "KalobaTuss® Children" for the Treatment of Cough in Children
Official title: Randomized, Controlled, Double Blind Clinical Study on the Assessment of Efficacy, Safety and Palatability of "KalobaTuss® Children", a Syrup for the Treatment of Cough in Pediatric Age (3-6 Years).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cough
Keywords: Persistent cough
Children
Lead sponsor: Azienda Ospedaliera Universitaria Policlinico "G. Martino"
Sponsor class: OTHER
First posted: 2019-08-29
Enrollment: 106
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind controlled clinical study .
Primary purpose: TREATMENT

Brief summary: Cough of children is one of the most frequent events for which parents ask for a medical consult and it is a true challenge for pediatrics during daily practice.

In the majority of cases, it is self-limiting, but its persistence could become exasperating and it could reduce quality of life and social activities.

Even if inappropriate prescription of antitussive pharmacological treatment in children has been reduced, pediatrics prescribing attitudes do not still always are reflecting accurate treatment of cough.

Furthermore, pediatric approach is always compromised by parental exaggerate perception of symptoms and usual consequent requirement of pharmacological prescription of antibiotics, that they consider the appropriate and effective therapeutic option for cough.

The World Health Organization identifies honey as a potential demulcent treatment for cough.

On the light of the above considerations and since available pediatric treatments for acute cough are limited by lack of demonstrated efficacy, a pediatric cough syrup product containing Acacia honey as well as specific fractions of resins, polysaccharides, saponins, flavonoids and sugars derived from Malva sylvestris extract, Inula helenium, Plantago major extract, Helichrysum stoechas (KalobaTuss) was developed to be clinically tested on persisting cough of children. Investigators evaluated through a randomized, double blind controlled clinical study the effects of KalobaTuss on persistent cough in children aging 3-6 years. The effects of Kalobatuss were compared with effects of placebo on nocturnal and daytime persistent cough for eight days. Objective of the study was to evaluate the clinical efficacy of KalobaTuss by using as primary endpoint the assessment of changes in day- and night-time cough score.

Detailed description: Cough of children is one of the most frequent events for which parents ask for a medical consult and it is a true challenge for pediatrics during daily practice. Cough is perhaps the most troubling symptom for children suffering from upper respiratory tract infections (URIs) and their parents. Often It results in discomfort to the child and loss of sleep for both children and parents.

In the majority of cases, persistent cough is self-limiting, but its persistence could become exasperating and it could reduce quality of life and social activities.

The influence of persistent cough of children on family's life can create growing discomfort. Indeed, children with acute cough may experience transient disability which leads to lose parents' work and school days so increasing overall cost for its management. Generally, parents' concerns increase when children's cough lasts for more than a week. Consequently, often occurs that parents seek for a medical consult with requirement of drug treatment, even if the most of antitussive drugs lack of proved evidence of effectiveness and safety.

Even if inappropriate prescription of antitussive pharmacological treatment in children has been reduced, pediatrics prescribing attitudes do not still always are reflecting accurate treatment of cough.

Furthermore, pediatric approach is always compromised by parental exaggerate perception of symptoms and usual consequent requirement of pharmacological prescription of antibiotics, that they consider the appropriate and effective therapeutic option for cough. Epidemiological data indicate that cough in children is much more feared than in adults and a substantial proportion of individuals think of cough as "a disease". Also a recent Italian survey confirms this view by suggesting that some pediatricians' therapeutic attitudes should be substantially improved in order to achieve better management of cough in children and to minimize the burden of cough. Moreover, it often happens that attempting to treat cough, children are administered with over-the-counter products having little or no scientific evidence of proven efficacy.

The World Health Organization identifies honey as a potential demulcent treatment for cough. Administration of honey before bedtime has been reported by parents as being preferable to dextromethorphan, diphenhydramine or placebo for symptomatic relief of their child's nocturnal cough and sleeping difficulty due to URIs. A separate clinical entity is cough when is without an organic cause. Such a persistent involuntary cough without a cause is considered to be a functional disorder.

On the light of the above considerations and since available pediatric treatments for acute cough are limited by lack of demonstrated efficacy, a pediatric cough syrup product containing Acacia honey as well as specific fractions of resins, polysaccharides, saponins, flavonoids and sugars derived from Malva sylvestris extract, Inula helenium, Plantago major extract, Helichrysum stoechas (KalobaTuss) to be clinically tested on persisting cough of children, has been developed. Researchers investigated through a randomized, double blind controlled clinical study the effects of KalobaTuss or placebo on persistent cough in children aging 3-6 years. Aim of this trial is to compare the effects of Kalobatuss with effects of placebo on nocturnal and daytime persistent cough for eight days.

Methods This randomized, double-blind controlled clinical study was carried out in the pediatric consulting rooms of the Azienda Ospedaliera Provinciale of Messina together with the Azienda ospedaliera Universitaria Policlinico "G. Martino of Messina, Italy. Children recruited for the study were divided in two groups: children belonging to the active group received the syrup KalobaTuss and the second group received a placebo as syrup formulation. Randomization was performed according to a table generated by Excel program. The double-blinding was released and the treatment groups to be revealed only after the analysis of the study results. Children aged between 3 and 6 years, with persistent cough for at least three consecutive days, which led parents to the need for medical consultation, participated in the study. Children with history of obstructive pulmonary diseases, cystic fibrosis, neuropathies, heart disease, diabetes and immunodeficiencies were excluded. Children suitable according to the inclusion criteria were randomly assigned to one of the treatment groups (KalobaTuss or placebo). Parents or tutors according children participation signed the informed consent form. The two treatment regimens were administered 4 doses a day, 5 ml each, for 8 days. The appearance, consistency, organoleptic characteristics and viscosity of KalobaTuss and placebo were similar.

The study was approved by the Ethic Committee of Azienda Ospedaliera Universitaria Policlinico "G. Martino" with protocol number 95/18 on 17 December 2018. The trial was conducted according to the ethical principles of the Seoul revision (2008) of the Helsinki Declaration and Good Clinical Practice.

Objective of the study was to evaluate the clinical efficacy of KalobaTuss by using as primary endpoint the evaluation and analysis of changes in day- and night-time cough score assessed through a questionnaire filled by parents. Cough was clinically diagnosed and evaluated by the pediatrician during the first visit and successively monitored by parents by filling a daily diary. At the end of the administration period pediatrician visited again children and collected the daily diary for each child.

The sample size was obtained assuming a mean cough score of 3 points in both groups at baseline, and a mean change in cough score of 2 and 1 points respectively for the arm treated with the study product and the placebo arm.

110 children with persistent cough were enrolled, 106 (96.36%) completed the treatment. 54 children received the KalobaTuss syrup and another 52 children received the placebo syrup. Four children, two from each group, left the study before the end of treatment.

The median age of children completing the study was 53.02 ± 12.02 months (range, 38-70 months; median age 4.3 months), with no significant difference in age between the two treatment arms (p= 0.8181).

54 children (50.8 %) were boys, of which 28 (51.85%) in the KalobaTuss syrup arm and 26 (48.15%) in the placebo arm. The mean duration of coughing before enrollment was 3.53 ± 0.57 (SD) for the KalobaTuss syrup and 3.52 ± 0.58 (SD) for the placebo arm, with no significant difference between the two arms (P= 0.93624). None of the children monitored for the study needed to receive antibiotics or any other pharmacological therapy during the days of treatment and for the follow-up period of one week after the end of the study.

Adverse events (AEs) were monitored during all the study period. An AE was defined as an inconvenient medical event occurring during the study period whether or not it was linked to the study procedure or the study product. A severe AE (SAE) was defined as a medical event resulting in death, a life-threatening situation, requiring inpatient admission or prolongation of hospitalization, and/or resulting in severe or persistent subject disability or incapacity.

Eligibility criteria: Inclusion Criteria:

* Healthy children aged between 3 and 6 years, with persistent cough for at least three consecutive days.

Exclusion Criteria:

* Children with history of obstructive pulmonary diseases, cystic fibrosis, neuropathies, heart disease, diabetes and immunodeficiencies were excluded.

Primary outcomes:
measure: Assessment of efficacy of treatment of cough persistent
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Messina
country: Italy
facility: Gioacchino Calapai
state: Me
Study officials:
affiliation: Azienda Ospedaliera Universitaria "G Martino", Messina, Italy.
name: Gioacchino Calapai, MD
role: PRINCIPAL_INVESTIGATOR
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