Testing of HIV Protease Inhibitors to Suppress Inflammation and Improve Cardio Pulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT02023450
• Date of registration: 23/12/2013
• Prospective Registration: No
• Primary sponsor: The Third Xiangya Hospital of Central South University
• Public title: Testing of HIV Protease Inhibitors to Suppress Inflammation and Improve Cardio Pulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension
• Date of first enrolment: December 2013
• Target sample size: 20
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT02023450
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 0

Countries of recruitment

China

Contacts

• Name: YU ZAI XIN, PhD

• Name: Li Ying, MD

Key inclusion & exclusion criteria

Inclusion Criteria:

- Age 18-60

- Idiopathic pulmonary arterial hypertension

- Evidence of a personally signed and dated informed consent document indicating that
the subject (or a legally acceptable representative) has been informed of all
pertinent aspects of the study

- Had the diagnosis of PAH confirmed by a cardiac catheterization:Mean pulmonary artery
pressure (mPAP) = 25 mm Hg (at rest),a pulmonary capillary wedge pressure equal or
less than 15mmHg, and a normal or reduced cardiac output

- Stable PAH therapy for at least 3 months

Exclusion Criteria:

- Baseline systemic hypotension, defined as MAP less than 50 mmHg

- Required intravenous inotropes within 30 days prior to study participation

- Has uncontrolled systemic hypertension as evidenced by sitting systolic blood
pressure >160 mm Hg or sitting diastolic blood pressure >100 mm Hg at screening

- Has a history of portal hypertension or chronic liver disease, including cirrhosis,
chronic alcoholism, hepatitis B and/or hepatitis C (with evidence of recent infection
and/or active virus replication) defined as moderate to severe hepatic impairment
(Child-Pugh Class B-C)

- Has chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL at
screening or requires dialysis support

- Has a hemoglobin concentration <9 g/dL at Screening

- History of atrial septostomy

- Repaired or unrepaired congenital heart disease (CHD)

- Pericardial constriction

- Restrictive or congestive cardiomyopathy

- Left ventricular ejection fraction 40% by multiple gated acquisition scan (MUGA),
angiography or echocardiography

- Symptomatic coronary disease with demonstrable ischemia

- Other severe acute or chronic medical or laboratory abnormality that may increase the
risk associated with study participation or investigational product administration or
may interfere with the interpretation of study results and, in the judgment of the
investigator, would make the subject inappropriate for entry into this study

- Has a psychiatric, addictive or other disorder that compromises the ability to give
informed consent for participating in this study. This includes subjects with a
recent history of abusing alcohol or illicit drugs 30 days prior to study screening
Day 1 and for the duration of the study

- Poorly controlled asthma defined by active wheezing and/or cough with FEV1 < 70%
predicted, responsive to inhaled BD (>15% increase in FEV1 with BD)

- Clinically significant intercurrent illness (including lower respiratory tract
infection) or clinically significant surgery within 4 weeks before the administration
of study drug

- History of hypersensitivity or idiosyncratic reaction to drugs from multiple drug
classes

- Receipt of an investigational product or device, or participation in a drug research
study within a period of 15 days (or 5 half lives of the drug, whichever is longer)
before the first dose of study drug

- Blood loss or blood donation >550mL within 90 days or plasma donation >500 mL within
14 days before administration of study drug;

- Patients with a QTc interval > 450 msec

- Has diabetes mellitus as defined by symptoms of hyperglycemia and serum fasting
plasma glucose level=7.0mmol/l or casual plasma glucose=11.1mmol/l at screen

- Has a hyperlipidemia as TC=6.22 mmol/L, LDL-C =4.14 mmol/L or TG =2.26 mmol/L

- History of crohn's disease, ulcerative colitis (UC) and etc. Inflammatory bowel
disease (IBD)

- Patients who are not willing to take contraceptive measures during the study

- Patients who are taking certain other medication will need to be evaluated for
possible exclusion based on the potential for adverse drug interactions



Age minimum: 18 Years
Age maximum: 60 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: saquinavir and ritonavir

Primary Outcome(s)

HMGB1 level [Time Frame: 14 days]

Secondary Outcome(s)

TNF?IL-1??IL-6?NT-ProBNP and CRP level [Time Frame: 14 days]

NYHA/WHO functional class [Time Frame: 14 days]

PA pressure and total right heart function measured by echocardiography [Time Frame: 14 days]

Brog respiration class [Time Frame: 14 days]

Secondary ID(s)

HPI-PAH-0

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Xiangya Hospital of Central South University