SPHERIC-1. Sildenafil and Pulmonary HypERtension In COPD (SPHERIC-1)

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

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.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Hypertension; COPD
• Intervention / Treatment: Drug: Sildenafil citrate; Drug: Sugar pills

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20162
    • Active, not recruiting
    • Pulmonary Unit - Azienda Ospedaliera Ospedale Niguarda Ca' Granda
  • Modena, Italy, 41100
    • Active, not recruiting
    • Pulmonary Diseases Clinic - Azienda Ospedaliera Universitaria - Policlinico di Modena
  • Napoli, Italy, 80131
    • Recruiting
    • Pulmonary Clinic - Federico II University - Azienda Ospedaliera V. Monaldi
    • Contact: Matteo Sofia, MD; Email: matteo.sofia@unina.it
  • Padova, Italy, 35128
    • Active, not recruiting
    • Thoracic Surgery Clinic - Azienda Ospedaliera di Padova
  • Palermo, Italy, 90127
    • Recruiting
    • Dept. of Medicine - Pulmonary Medicine - IsMeTT
    • Contact: Patrizio Vitulo, MD; Phone Number: 00390912192111; Email: pvitulo@ismett.edu
  • Pavia, Italy, 27100
    • Recruiting
    • Pulmonary Diseases Clinic - Fondazione IRCCS Policlinico San Matteo
    • Contact: Tiberio Oggionni, MD; Email: t.oggionni@smatteo.pv.it
  • Rome, Italy, 00161
    • Recruiting
    • Pulmonary Hypertension Center - Policlinico Umberto I
    • Contact: Carmime D. Vizza, MD; Phone Number: 00390649979051; Email: dario.vizza@uniroma1.it
  • Siena, Italy, 53100
    • Recruiting
    • University Pulmonary Unit - Azienda Ospedaliera Universitaria Senese
    • Contact: Paola Rottoli, MD; Email: rottoli@unisi.it
  • Torino, Italy, 10143
    • Recruiting
    • Pulmonary Unit - Azienda Ospedaliera Universitaria San Giovanni Battista
    • Contact: Daniela Libertucci, MD; Email: dlibertucci@molinette.piemonte.it
  • Trieste, Italy, 34100
    • Recruiting
    • Pulmonary Unit - Azienda Ospedaliera Universitaria Ospedali Riuniti di Trieste
    • Contact: Marco Confalonieri, MD; Email: marco.confalonieri@aots.sanita.fvg.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar pill	Drug: Sugar pills; placebo t.i.d.
Active Comparator: Sildenafil citrate; 20 mg t.i.d.	Drug: Sildenafil citrate; sildenafil 20 mg t.i.d. compared to placebo 20 mg t.i.d - 16 weeks treatment; Other Names: Revatio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary vascular resistance (PVR)	PVR are measured by right cath study as the following formula: PVR= (mean pulmonary arterial pressure-pulmonary arterial wedge pressure)/cardiac output	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial blood gas analysis		16 Weeks
Pulmonary function - Borg scale	The dyspnea is assessed by an analogic scale from 0 (no dyspnea) to 10 (very severe dyspnea)	16 Weeks
Pulmonary function - Bode Index	The BODE Index is a composite marker of disease taking into consideration the systemic nature of COPD: FEV1% pred = predicted amount as a percentage of the forced expiratory lung volume in one second; 6MWD = six minute walking distance; MMRC = modified medical research council dyspnea scale; BMI = body mass index.	16 Weeks
Functional capacity - Quality of Life	Quality of Life is assessed by a standardized questionnaire (SF-36 questionnaire) at baseline and the end of study	16 Weeks
Functional capacity testing - 6 Minutes walking test	The six-minute walk test is performed in a straight corridor (length 25-30 meters) in the same environmental conditions	16 Weeks

Collaborators and Investigators

• Sponsor: Italian Association of Hospital Pneumologists
• Investigators: Study Chair: Patrizio Vitulo, MD, Dept. of Medicine - Pulmonary Medicine - IsMeTT Palermo, Italy; Study Chair: Carmine D. Vizza, MD, Pulmonary Hypertension Center - Dept. of Cardiovascular and Respiratory Sciences - I° School of Medicine - Sapienza University of Rome (Italy)

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Anticipated): February 1, 2013
• Study Completion (Anticipated): February 1, 2013

Study Registration Dates

• First Submitted: July 29, 2011
• First Submitted That Met QC Criteria: September 27, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Estimate): February 4, 2013
• Last Update Submitted That Met QC Criteria: February 1, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: ARC209