SPHERIC-1. Sildenafil and Pulmonary HypERtension In COPD

COPD Clinical Trial

— SPHERIC-1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01441934
• Other study ID #: ARC209
• Status: Recruiting
• Phase: Phase 3
• First received: July 29, 2011
• Last updated: February 1, 2013
• Start date: October 2010
• Est. completion date: February 2013

Study information

• Verified date: February 2013
• Source: Italian Association of Hospital Pneumologists
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• COPD
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Disease, Chronic Obstructive
• Pulmonary Hypertension

Intervention

Drug:
• Sildenafil citrate
sildenafil 20 mg t.i.d. compared to placebo 20 mg t.i.d - 16 weeks treatment
• Sugar pills
placebo t.i.d.

Locations

Country	Name	City	State
Italy	Pulmonary Unit - Azienda Ospedaliera Ospedale Niguarda Ca' Granda	Milano
Italy	Pulmonary Diseases Clinic - Azienda Ospedaliera Universitaria - Policlinico di Modena	Modena
Italy	Pulmonary Clinic - Federico II University - Azienda Ospedaliera V. Monaldi	Napoli
Italy	Thoracic Surgery Clinic - Azienda Ospedaliera di Padova	Padova
Italy	Dept. of Medicine - Pulmonary Medicine - IsMeTT	Palermo
Italy	Pulmonary Diseases Clinic - Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Pulmonary Hypertension Center - Policlinico Umberto I	Rome
Italy	University Pulmonary Unit - Azienda Ospedaliera Universitaria Senese	Siena
Italy	Pulmonary Unit - Azienda Ospedaliera Universitaria San Giovanni Battista	Torino
Italy	Pulmonary Unit - Azienda Ospedaliera Universitaria Ospedali Riuniti di Trieste	Trieste

Sponsors (1)

Lead Sponsor	Collaborator
Italian Association of Hospital Pneumologists

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Arterial blood gas analysis		16 Weeks	Yes
Secondary	Pulmonary function - Borg scale	The dyspnea is assessed by an analogic scale from 0 (no dyspnea) to 10 (very severe dyspnea)	16 Weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No