Study of the Initial Combination of Bosentan With Iloprost in the Treatment of Pulmonary Hypertension Patients (BIPH)

Phase Ⅲ Study of the Initial Combination of Bosentan With Iloprost in the Treatment of Pulmonary Arterial Hypertension Patients

Previous studies suggest that combinations of existing therapies may be effective for pulmonary arterial hypertension (PAH). However, all of these studies are sequential combination therapy, for example, by adding sildenafil to previously prescribed bosentan. This kind of therapy model is not enough for PAH patients, especially those with New York Heart Association (NYHA) class Ⅲ and Ⅳ. In this randomized, multicenter study, the investigators evaluate the safety and efficacy of combining inhaled iloprost, a prostacyclin analog, with the endothelin receptor antagonist bosentan in treatment naive patients with PAH by comparing with bosentan monotherapy. Efficacy endpoints include change from baseline in 6-min-walk distance (6-MWD), modified (NYHA) functional class, hemodynamic parameters, and time to clinical worsening.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Bosentan; Drug: Iloprost

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shengqing Li, MD, PhD; Phone Number: +86-29-84771132; Email: shengqingli@gmail.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • The department of pulmonary and critical care medicine, Tangdu hospital
      • Contact: Yonghong Xie, MD; Phone Number: +86-29-84777725; Email: xieyh65@yahoo.com.cn
      • Principal Investigator: Yonghong Xie, MD
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • The department of pulmonary and critical care medicine, Xijing hospital
      • Contact: Xinpeng Han, MD; Phone Number: +86-29-84775237; Email: hxp0728@163.com
      • Sub-Investigator: Xinpeng Han, MD
      • Sub-Investigator: Yongping Yu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 78 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged 10 to 80
• treatment naive symptomatic PAH
• 6-MWD of 100-425 m
• resting mean pulmonary artery pressure greater than 25 mm Hg, pulmonary capillary wedge pressure less than 15 mm Hg, and pulmonary vascular resistance of 240 dyn.s.cm-5 or greater.

Exclusion Criteria:

• Patients with thromboembolic disease,
• untreated obstructive sleep apnea,
• portal hypertension,
• chronic liver disease or renal insufficiency,
• left-sided or unrepaired congenital heart disease,
• substantial obstructive (FEV1/FVC<50% predicted) or restrictive (total lung capacity<60% predicted) lung disease
• Patients receiving phosphodiesterase inhibitors or other prostanoids and endothelin receptor antagonists

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination therapy; combine inhaled iloprost, 10μg, 4-6times/day with bosentan,125mg,po,bid.	Drug: Bosentan; Drug: Iloprost
Active Comparator: monotherapy; Bosentan,125mg,po,bid.	Drug: Bosentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change from baseline in 6-min-walk distance (6-MWD)	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
modified (NYHA) functional class	12 weeks

Other Outcome Measures

Outcome Measure	Time Frame
time to clinical worsening	2 years

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China
• Investigators: Principal Investigator: Shengqing Li, MD, PhD, The department of pulmonary and critical care medicine, Xijing hospital

Publications and helpful links

General Publications

• Han X, Zhang Y, Dong L, Fang L, Chai Y, Niu M, Yu Y, Liu L, Yang X, Qu S, Li S. Treatment of Pulmonary Arterial Hypertension Using Initial Combination Therapy of Bosentan and Iloprost. Respir Care. 2017 Apr;62(4):489-496. doi: 10.4187/respcare.05280. Epub 2017 Jan 24.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: October 22, 2012
• First Submitted That Met QC Criteria: October 23, 2012
• First Posted (Estimate): October 24, 2012

Study Record Updates

• Last Update Posted (Estimate): February 27, 2014
• Last Update Submitted That Met QC Criteria: February 26, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Treatment of
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Platelet Aggregation Inhibitors; Endothelin Receptor Antagonists; Iloprost; Bosentan
• Other Study ID Numbers: BIPH-20121022