SPHERIC-1. Sildenafil and Pulmonary HypERtension In COPD

This study is currently recruiting participants.
Verified February 2013 by Italian Association of Hospital Pneumologists
Sponsor:
Information provided by (Responsible Party):
Dr. Patrizio Vitulo, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
ClinicalTrials.gov Identifier:
NCT01441934
First received: July 29, 2011
Last updated: February 1, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Pulmonary Hypertension
COPD
Drug: Sildenafil citrate
Drug: Sugar pills
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Italian Association of Hospital Pneumologists:

Primary Outcome Measures:
  • Pulmonary vascular resistance (PVR) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

    PVR are measured by right cath study as the following formula:

    PVR= (mean pulmonary arterial pressure-pulmonary arterial wedge pressure)/cardiac output



Secondary Outcome Measures:
  • Arterial blood gas analysis [ Time Frame: 16 Weeks ] [ Designated as safety issue: Yes ]
  • Pulmonary function - Borg scale [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    The dyspnea is assessed by an analogic scale from 0 (no dyspnea) to 10 (very severe dyspnea)

  • Pulmonary function - Bode Index [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    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.

  • Functional capacity - Quality of Life [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    Quality of Life is assessed by a standardized questionnaire (SF-36 questionnaire) at baseline and the end of study

  • Functional capacity testing - 6 Minutes walking test [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    The six-minute walk test is performed in a straight corridor (length 25-30 meters) in the same environmental conditions


Estimated Enrollment: 32
Study Start Date: October 2010
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Revatio
Placebo Comparator: Sugar pill Drug: Sugar pills
placebo t.i.d.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01441934

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

No publications provided

Responsible Party: Dr. Patrizio Vitulo, Head of Pulmonary Medicine, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
ClinicalTrials.gov Identifier: NCT01441934     History of Changes
Other Study ID Numbers: ARC209
Study First Received: July 29, 2011
Last Updated: February 1, 2013
Health Authority: Italy: Ethics Committee
Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 14, 2014