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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01441934
Recruitment Status : Unknown
Verified February 2013 by Dr. Patrizio Vitulo, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies.
Recruitment status was:  Recruiting
First Posted : September 28, 2011
Last Update Posted : February 4, 2013
Information provided by (Responsible Party):
Dr. Patrizio Vitulo, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension COPD Drug: Sildenafil citrate Drug: Sugar pills Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : October 2010
Estimated Primary Completion Date : February 2013
Estimated Study Completion Date : February 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Pulmonary vascular resistance (PVR) [ Time Frame: 16 weeks ]

    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 :
  1. Arterial blood gas analysis [ Time Frame: 16 Weeks ]
  2. Pulmonary function - Borg scale [ Time Frame: 16 Weeks ]
    The dyspnea is assessed by an analogic scale from 0 (no dyspnea) to 10 (very severe dyspnea)

  3. Pulmonary function - Bode Index [ Time Frame: 16 Weeks ]
    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.

  4. Functional capacity - Quality of Life [ Time Frame: 16 Weeks ]
    Quality of Life is assessed by a standardized questionnaire (SF-36 questionnaire) at baseline and the end of study

  5. Functional capacity testing - 6 Minutes walking test [ Time Frame: 16 Weeks ]
    The six-minute walk test is performed in a straight corridor (length 25-30 meters) in the same environmental conditions

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01441934

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   
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   
Pulmonary Diseases Clinic - Fondazione IRCCS Policlinico San Matteo Recruiting
Pavia, Italy, 27100
Contact: Tiberio Oggionni, MD   
Pulmonary Hypertension Center - Policlinico Umberto I Recruiting
Rome, Italy, 00161
Contact: Carmime D. Vizza, MD    00390649979051   
University Pulmonary Unit - Azienda Ospedaliera Universitaria Senese Recruiting
Siena, Italy, 53100
Contact: Paola Rottoli, MD   
Pulmonary Unit - Azienda Ospedaliera Universitaria San Giovanni Battista Recruiting
Torino, Italy, 10143
Contact: Daniela Libertucci, MD   
Pulmonary Unit - Azienda Ospedaliera Universitaria Ospedali Riuniti di Trieste Recruiting
Trieste, Italy, 34100
Contact: Marco Confalonieri, MD   
Sponsors and Collaborators
Italian Association of Hospital Pneumologists
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)

Responsible Party: Dr. Patrizio Vitulo, Head of Pulmonary Medicine, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies Identifier: NCT01441934     History of Changes
Other Study ID Numbers: ARC209
First Posted: September 28, 2011    Key Record Dates
Last Update Posted: February 4, 2013
Last Verified: February 2013

Additional relevant MeSH terms:
Hypertension, Pulmonary
Pulmonary Disease, Chronic Obstructive
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Citric Acid
Sildenafil Citrate
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents