E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
acute exacerbation of chronic obstructive pulmonary disease (AE-COPD)
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010953 |
E.1.2 | Term | COPD exacerbation |
E.1.2 | System Organ Class | 100000004855 |
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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 |
To demonstrate in a clinical study that there is no relevant increase in the “failure-rate” for patients with acute moderate exacerbations of COPD (AE-COPD) treated with placebo instead of antibiotic treatment both on top of standard of care. A patient is classified as treatment failure if additional antibiotic therapy is required during treatment period or until the test of cure visit |
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E.2.2 | Secondary objectives of the trial |
•To evaluate long-term consequences of Placebo treatment -Relapse rate at late follow-up 1 -Time to relapse •To assess patient’s clinical improvement relative to treatment -Clinical cure rate at the EOT visit -Clinical cure rate at the TOC visit To assess additional efficacy endpoints and health outcome evaluations following 5 days treatment with either placebo or oral sultamicillin with either treatment used as a supplement to the standard of care for patients with acute exacerbations of COPD: -Changes in CAT -Changes in EXACT PRO -Changes in relevant systemic biomarkers and their association to mortality -Additional antibiotic therapy -Time to next exacerbation -Number of exacerbations during follow up -Per-subject relapse rate at the LFU visits in the subset of subjects in the CE population who were clinically cured at the TOC visit -Changes in length of stay in hospital for hospitalized patients -All cause mortality
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adults, either sex, older than 40 years of age • For female patients, the following conditions are to be met: - has been postmenopausal for at least 1 year, or - is surgically incapable of bearing children, or - is of childbearing potential, and the following conditions are met: o has a negative pregnancy test (urine- or serum-based) immediately before study entry (i.e., before the start of treatment or any other study procedure that could potentially harm the fetus), and one or more of following criteria o must agree to abstinence or use an accepted method of contraception .The subject must agree to continue with the same method throughout the study. o having only female sexual partners o sexual relationship with sterile male partners only • Patients diagnosed with COPD stages I-IV as defined by the Global initiative for chronic Obstructive Lung disease (GOLD). and • Doctor's diagnosis of acute (onset < 7 days) moderate exacerbation of COPD defined by a sustained worsening of the patient’s condition (including at least 2 of the following symptoms: increased dyspnea, increased sputum production, sputum purulence and increased cough), from the stable state and beyond normal day-to-day variations, necessitating a change in regular medication in patient with underlying COPD, needing additional medical assistance. • Absence of community acquired pneumonia or lower respiratory tract infection with a clear indication for antibiotic treatment as determined by Procalcitonin level < 0.25 ng/mL and/or absence of pulmonary infiltrates on routine chest x-ray. • Smoking history of at least 10 Pack Years or more. • Patients must sign and date an informed consent prior to any study procedures.
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E.4 | Principal exclusion criteria |
• Severe exacerbation: defined by need for ventilatory support (indicated by severe dyspnea with failure to respond to emergency treatment and/or persistent hypoxemia (PaO2 <50 mm Hg despite O2 administration and / or respiratory acidosis (pH <7.35 and PaCO2> 45mmHg)) or mental confusion or circulatory insufficiency (need of vasopressors) • Fever (>38.5°C) (more than 4 days) • Known impaired hepatic or renal function • Active or suspected tuberculosis infection of the respiratory tract • Acute exacerbation of asthma • Suspected or known hypersensitivity to, or suspected serious adverse reaction to Sultamicillin • Immunosuppression or Immunosuppressive therapy (cytostatic chemotherapy within last 28 days or neutropenia (neutrophils < 1000/µ)l; systemic corticosteroids (≥20 mg prednisolon equivalent/day > 14 days; HIV-infection; immunosuppression after organ- or bone marrow transplant)- Patients with metastatic or hematological malignancy, splenectomized patients or patients with known hyposplenia or asplenia • Oral/parenteral antibiotic use within 30 days prior to randomization (a singular administration of antibiotics prior to randomization is allowed) • In-patient treatment within the last 30 days days (because of actual respiratory infections as primary or secondary diagnosis) • An antibiotic is clearly indicated for treatment of a known infection • Known MRSA colonization or infection • Patients with known bronchiectasis • Patients with known bacterial airway colonization (>3 positive sputum cultures in the previous year) • Progressively fatal disease, or life expectancy ≤6 months • Mononucleosis • Lymphatic leukemia • Severe gastro-intestinal disorders with vomiting and diarrhea • Women who are breast feeding • Patients who have received treatment with any other investigational drug within 1 month prior to study entry, or have such treatment planned for the study period during treatment and follow up phase. • Patients with mental conditions rendering them unable to understand the nature, scope, and possible consequences of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of additional antibiotic therapy during treatment period or until the test of cure visit
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. treatment period (during 5 days after start of treatment) 2. Test of cure (TOC) visit:4 weeks after start of treatment |
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E.5.2 | Secondary end point(s) |
Relapse rate at late follow-up (LFU-2; 1 year) and time to relapse clinical cure rate at the EOT visit and clinical cure rate at the TOC visit (both determined by patient-centered outcomes (diary cards assessed daily for 4 weeks) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Relapse rate: 1 year after the start of treatment (late follow up 2 (LFU-2)) 2. time to relapse clincal cure rate: after 6 days (EOT Visit) 3. clinical cure rate: 4 weeks after start of treatment (TOC visit)
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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) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 32 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |