E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Chronic inflammation of palatine tonsils |
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E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009152 |
E.1.2 | Term | Chronic tonsillitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to assess the therapeutic effectiveness of Tonsilotren in the treatment of chronic tonsillitis when used in addition to conventional symptomatic treatment (test group) in comparison to conventional symptomatic treatment alone (control group). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to assess safety and tolerability of Tonsilotren treatment in chronic tonsillitis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females aged from 6 to 60 years;
2. Diagnosed chronic tonsillitis characterized by:
- the presence of at least three of five local symptoms at visit 1:
o Hyperemia of the anterior palatine arches;
o Edema of angle where the anterior and posterior palatine arches join each other;
o Caseous purulent plug and / or purulent exudates in the tonsillar crypts;
o Friable tonsils or indurated tonsils or scarred adhesions between the tonsils and the palatine arches;
o Enlarged submandibular lymph nodes.
- At least three acute throat infections within the past twelve months, or two acute throat infections during each of the two last years, documented in the patient file;
Definition and criteria for accepted documentation of acute throat infection in the patient file: Diagnoses and / or corresponding codes J02 and J03 according to WHO ICD-10. Also documentation in referral letters is accepted. If exact number of events is not given, information (date and diagnosis of each event) should be obtained by contact with referral person and documented.
3. Signed informed consent according to the applicable law;
4. Willingness and ability to comply with all procedures of the trial.
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E.4 | Principal exclusion criteria |
1. Presence of acute throat infection at inclusion;
2. Presence of peri-tonsillar abscess;
3. Presence of acute and chronic otitis, adenoiditis, sinusitis of all types, odontological infection, bronchial and lung disease (e.g. bronchitis, bronchial asthma, cystic fibrosis), tuberculosis or known allergic manifestations in the throat and / or mouth;
4. Obstruction in the pharynx due to enlargement of tonsils (causing severe sleep disorders e.g. sleep apnea);
5. Presence of severe cardiovascular, renal or hepatic disease, as well as gastroesophageal reflux, unstable diabetes mellitus, hyperthyroidism, cerebrovascular or other active bleeding, Human Immunodeficiency Virus (HIV) infection, mononucleosis of each severity, or oropharyngeal gonorrhea;
6. History of non-steroidal anti-inflammatory drugs (NSAIDs) intolerance (e.g. bronchospasm, asthma, rhinitis, urticaria, gastrointestinal bleeding or perforation), hematogenetic dysfunction of unknown origin, repeated peptic ulcera or hemorrhages;
7. History or presence of all kind of serious streptococcal complications (rheumatic heart disease, glomerulonephritis, joint pain, arthritis);
8. Previous surgery in the past six months or need for surgery of the nose or paranasal sinuses, adenoids and / or tonsils;
9. Evidence of any malignant disease during the past five years before enrolment into the trial;
10. Presence of neurological and / or psychiatric diseases (e.g. depressive episode) interfering with evaluation of quality of life and assessment in the patient's diary;
11. Treatment with systemic acting antibiotics, glucocorticosteroids or medications with immunomodulating activities during the past four weeks and treatment with NSAIDs as well as locally on the tonsils acting antibiotics, glucocorticosteroids or immunomodulators during the past week prior to enrolment into the trial;
12. Known or suspected hypersensitivity to chromium, mercury or any other ingredient and / or excipient of Tonsilotren as well as lactose and / or fructose intolerance and known intolerance towards leather and jewelry metals as well as towards dental metal fillings and vaccines;
13. Heavy smoking (>= 20 cigarettes per day) or known or suspicion to or presence of drug addiction including alcohol abuse;
14. Women of childbearing potential without adequate contraception or women, who want to become pregnant, are pregnant or breast-feeding;
15. Prior enrolment into this trial;
16. Participation in another clinical trial during the past three months prior to enrolment into the trial;
17. Incapability of understanding nature, meaning and consequences of the trial;
18. Patients in custody by juridical or official order;
19. Patients, who are members of the staff of the study center, staff of the sponsor or involved Clinical Research Organizations (CROs), the investigator him- / herself or close relatives of the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Mean period of time between consecutive acute throat infections within one year.
An acute throat infection must be confirmed by the investigator. It is defined by the presence of fever (axillary temperature >= 37.5°C), throat hyperemia (e.g. pharynx, tonsils, etc.) and difficulty in swallowing / sore throat.
Patients are instructed to visit their investigator for an additional visit in case they feel sick with acute complaints in the upper respiratory tract. Investigators are requested to document primary diagnosis. Acute throat infections are limited to all diagnoses in accordance with codes J02 and J03 of WHO ICD-10 (e.g. acute pharyngitis, acute tonsillitis, adenotonsillitis, or tonsillopharyngitis) and may be of viral or bacterial origin.
Relapses of acute throat infection within 7 days after end of its treatment belong to the originating acute throat infection and do not count separately.
Time between two acute throat infections will be calculated using first day of infection as reference point.
Evaluation year is defined as period between visit 3 (week 8) and visit 9 (week 60). Withdrawals until visit 3 will be replaced.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
2. Number of days with either sore throat / difficulties in swallowing or halitosis or exhaustion (infection-related complaints e.g. fatigue, weakness, sleeping disorders, decreased appetite, lack of concentration or decreased productivity) on the basis of patient diary in each single treatment period and each follow-up period;
3. Number of URTIs within one year ;
4. Severity of chronic tonsillitis symptoms as evaluated by the investigator at each regular study visit ;
5. Frequency of antibiotics consumption due to acute throat infections;
6. Days with analgetics consumption due to acute throat infections;
7. Effect of treatment on performance of normal daily activity in each single treatment and each follow-up period based on the information given in the patient's diary;
8. Patient's quality of life using a 5-item rating scale (very good, good, moderate, poor, very poor) at each regular visit except visit 2;
9. Treatment outcome according to Integrative Medicine Outcome Scale (IMOS) at each post-baseline study visit except visit 2;
10. Tolerability of treatment at the end of each study treatment period (evaluation in test group only);
11. Adverse events including incidence of tonsillitis’ complications (rheumatic fever, rheumatic heart disease, glomerulonephritis, arthritis).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to each individual endpoint, see section E.5.2. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Add-on trial: all patients: conventional symptomatic treatment, test group additionally Tonsilotren. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Conventional symptomatic treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Time point of study data base closure. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |