E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease Pulmonary hypertension (secondary to chronic obstructive pulmonary disease) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Contains |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037406 |
E.1.2 | Term | Contains |
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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 |
Do these drugs make bronchitic patients able to walk further before they have to stop? |
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E.2.2 | Secondary objectives of the trial |
Do these drugs improve the quality of life of bronchitic patients? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
INCLUSION CRITERIA Men and women age 35-85 years suffering from moderate to severe COPD (FEV1 <80% of predicted), who are smokers or ex-smokers with a history of at least 20 pack years (GOLD criteria stage II-III). Echocardiography will be used to assess whether they have pulmonary hypertension or not. Two echo criteria will be used. The first one will be right ventricular systolic pressure (RVSP) which is considered equal to systolic pulmonary artery pressure in the absence of pulmonary valve stenosis. RVSP is recommended in guidelines from the ACCP to detect pulmonary hypertension. The precise technique of measuring RVSP by Doppler echocardiography is described by McGoon et al. Briefly, the velocity of the tricuspid regurgitant (TR) jet is calculated (v) and computed along with the right atrial pressure (RAP) as follows: RVSP = 4v2 + RAP. Patients will be included if their RVSP >30mmHg. The reliability of RVSP estimated from echo TR has been studied repeatedly: McGoon et al (2004) quote 10 such studies where echo RVSP correlated well with right heart catheterisations in nine out of these ten studies. Indeed, the ACCP guidelines say “In patients with a clinical suspicion of pulmonary hypertension, Doppler echocardiography should be performed to evaluate the level of RVSP”. However, RVSP is only able to be calculated in 60-70% of COPD cases and an alternative is the pulmonary acceleration time which is a measure of mean pulmonary artery pressure (MPAP). This is obtainable in 40-50% of COPD individuals in our experience. It has good reproducibility and correlates well with catheter derived measures. Prof Lipworth (co-applicant) has been using both measures for over 10 years. Cardiac output will also be assessed echocardiographically. For inclusion, patients will need to have a reduced pulmonary acceleration time (<120 ms) which equates to an MPAP >20 mmHg. Since these two echo measures should be very close, we will recruit only those with an RVSP >30 mmHg and a pulmonary acceleration time <120 ms, although if one of these measures is unmeasurable, they can be recruited on the basis of the other one alone. This is a pragmatic approach reflecting that the real world of clinical practice/research is not the same as the ideal world. Patients with fluid retention (Cor Pulmonale) will be recruitable as long as they appear euvolaemic on clinical examination due to diuretic therapy. |
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E.4 | Principal exclusion criteria |
EXCLUSION CRITERIA Pulmonary stenosis or echo LV outflow obstruction or LV systolic dysfunction (LVEF <45%). Patients taking nitrates, nicorandil or doxazosin will also be excluded. Other standard contraindications for such drugs will apply, e.g. systolic BP <90 mmHg, recent stroke, unstable angina, past history of non arteritic anterior ischaemic optic neuropathy. With all these exclusions applied, PDE5A inhibitors such as tadalafil are regarded as safe.
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
E.6.5 | Efficacy | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
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.8.3 |
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 | 2 |
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 | Information not present in EudraCT |
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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Last visit of last subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |