Do Phosphodiesterase 5 Inhibitors Improve Exercise Capacity in COPD Patients with Pulmonary Hypertension? - The 3P study

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 120

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Do these drugs make bronchitic patients able to walk further before they have to stop?;Secondary Objective: Do these drugs improve the quality of life of bronchitic patients?;Primary end point(s): Six minute walk test

Secondary Outcome Measures

Name	Time	Method

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