Clinical trial NCT01441934: SPHERIC-1. Sildenafil and Pulmonary HypERtension In COPD
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Effect of Sildenafil in the Treatment of Patients With Pulmonary Hypertension Associated to Chronic Obstructive Lung Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pulmonary Hypertension
COPD
Lead sponsor: Italian Association of Hospital Pneumologists
Sponsor class: OTHER
First posted: 2011-09-28
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Although pulmonary hypertension (PH) is a quite frequent complication of advanced pulmonary diseases, and it is an independent prognostic factor, until now no evidence-based treatment approach exists for those patients.

This study will address if the drug sildenafil can lower pulmonary vascular resistance in patients with significant pulmonary hypertension (high blood pressure in the lungs) associated to chronic obstructive pulmonary disease (COPD). It will see if this treatment can improve effort capacity, quality of life without causing a deterioration in pulmonary gas exchange (mainly arterial oxygenation).

Patients 18 years of age and older with moderate COPD and pulmonary hypertension (mean pulmonary arterial pressure \>30 mmHg) may be eligible for this study. Participants are randomly assigned to receive sildenafil or placebo (pill with no drug) for 16 weeks.

Before starting treatment (baseline), and a the end of the study, the patients have a comprehensive assessment including:

* a chest x-ray and CT scan (only at baseline);
* pulmonary function tests to measure how much air the patient can breathe in and out, and the capacity of diffusion of gases;
* arterial blood gases analysis (for safety reason this examination is performed at baseline, before the randomization after one hour from the administration of a tablet (20 mg) of sildenafil, and every month)
* an echocardiogram (heart ultrasound) (only at baseline);
* a 6-minute walk test to measure exercise capacity;
* a quality-of-life assessment (SF-36 questionnaire)
* a right heart catheterization to evaluate the severity of hypertension

At the end of the 16-week period, patients may opt to continue to receive sildenafil and monitoring in an open-label phase of the study for up to 1 year.


Eligibility criteria: Inclusion Criteria:

* Patient affected by stable COPD under optimal treatment, chronic oxygen therapy in patients with hypoxia, with PaO2 at rest ≥ 60 mmHg and PaCO2≤ 55 mmHg, aged between 18 and 80 years old:
* Group 1: BPCO GOLD I-III (post bronchodilator FEV1 ≥ 30%, FEV1/FVC ≤ 0,7 , TLC ≥ 70%) + PAPm ≥ 30 mmHg and PCP \<15 mmHg
* Group 2: BPCO GOLD IV (post bronchodilator FEV1 \<30%, FEV1/FVC ≤ 0,7 , TLC ≥ 70%) + PAPm ≥ 35 mmHg and PCP \<15 mmHg

Exclusion Criteria:

* Different types of pulmonary hypertension (chronic, thromboembolic pulmonary hypertension, pulmonary arterial hypertension etc.)
* Significant left cardiac disease (LVEF \<45%, cardiomyopathy, valvulopathy, unstable coronaropathy)
* Treatment with nitrates in the last 10 days, or in need of other nitrate therapy for different diseases
* Treatment with other specific drugs for arterial pulmonary hypertension (less than 4 weeks)
* Significant systemic disease other than COPD
* Recent exacerbations of chronic bronchitis (\< 4 weeks)
* Pregnancy or breastfeeding, or women without an adequate contraceptive method for the whole study duration
* History of anaphylaxis or allergic reactions to 5-phosphodiesterase inhibitors
* Cancers within the last 5 years with the exception of localized cancers of the skin or of the cervix
* Hepatic insufficiency or chronic renal failure or hemoglobinemia \< 10 g/dL during the screening phase
* Contraindications to subministration as per SPC
* Mental disorder, alcohol abuse, chronic alcoholism, drug abuse
* Subjects unable to sign the informed consent form
* Subjects unable to walk

Primary outcomes:
measure: Pulmonary vascular resistance (PVR)
timeFrame: 16 weeks
Secondary outcomes:
measure: Arterial blood gas analysis
timeFrame: 16 Weeks
measure: Pulmonary function - Borg scale
timeFrame: 16 Weeks
measure: Pulmonary function - Bode Index
timeFrame: 16 Weeks
measure: Functional capacity - Quality of Life
timeFrame: 16 Weeks
measure: Functional capacity testing - 6 Minutes walking test
timeFrame: 16 Weeks
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Pulmonary Unit - Azienda Ospedaliera Ospedale Niguarda Ca' Granda
city: Modena
country: Italy
facility: Pulmonary Diseases Clinic - Azienda Ospedaliera Universitaria - Policlinico di Modena
city: Napoli
country: Italy
facility: Pulmonary Clinic - Federico II University - Azienda Ospedaliera V. Monaldi
city: Padova
country: Italy
facility: Thoracic Surgery Clinic - Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: Dept. of Medicine - Pulmonary Medicine - IsMeTT
city: Pavia
country: Italy
facility: Pulmonary Diseases Clinic - Fondazione IRCCS Policlinico San Matteo
city: Rome
country: Italy
facility: Pulmonary Hypertension Center - Policlinico Umberto I
city: Siena
country: Italy
facility: University Pulmonary Unit - Azienda Ospedaliera Universitaria Senese
city: Torino
country: Italy
facility: Pulmonary Unit - Azienda Ospedaliera Universitaria San Giovanni Battista
city: Trieste
country: Italy
facility: Pulmonary Unit - Azienda Ospedaliera Universitaria Ospedali Riuniti di Trieste
Study officials:
affiliation: Dept. of Medicine - Pulmonary Medicine - IsMeTT Palermo, Italy
name: Patrizio Vitulo, MD
role: STUDY_CHAIR
affiliation: Pulmonary Hypertension Center - Dept. of Cardiovascular and Respiratory Sciences - I° School of Medicine - Sapienza University of Rome (Italy)
name: Carmine D. Vizza, MD
role: STUDY_CHAIR
References: