The effects of epidermal growth factor receptor inhibition on pulmonary arterial hypertension associated with systemic sclerosis

Completed

Conditions: Sclerosis-associated Pulmonary Arterial Hypertension (SScPAH)
Circulatory System
Pulmonary Arterial Hypertension

Registration Number: ISRCTN75611179

Lead Sponsor: VU University Medical Centre (The Netherlands)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 20

Inclusion Criteria

A subject is eligible for inclusion in this study only if all of the following criteria apply:
1. Written informed consent
2. Systemic sclerosis
3. Pulmonary Arterial Hypertension (PAH) with a mean Pulmonary Arterial Pressure (PAP) of above 25 mmHg measured during rest
4. Pulmonary Vascular Resistance (PVR) above 300 dynes
5. Total Lung Capacity (TLC) more than 70%
6. New York Heart Association (NYHA) class III and/or six-Minute Walk Test (6-MWT) less than 80% predicted
7.Conventional PAH treatment and/or bosentan and/or sildenafil treatment
8. Stability on medication during the previous three months (defined as stable or decrease of 6-MWT after three months of treatment)

Exclusion Criteria

A subject will be excluded from this study in case of the following criteria:
1. Left ventricular dysfunction
2. Valvular heart disease
3. Pericardial constriction
4. Wedge pressure more than or equal to 15 mmHg
5. Chronic thromboembolic pulmonary hypertension
6. Uncontrolled sleep apnea
7. History of malignancies
8. Overt right heart failure
9. History or presence of skin ulcerations
10. Women Of Child-Bearing potential (WOCB) who are unwilling or unable to use contraceptives
11. Sexually active fertile man not using effective birth control if their partners are WOCB
12. Severe abnormality of the cornea
13. Inadequate haematologic function defined by an absolute neutrophil count less than 1,500/mm^3, platelet count less than 80,000/mm^3 and haemoblobin level of less than 9 g/dL
14. Inadequate hepatic function defined by a total bilirubin level 1.5 times the Upper Limit of Normal (ULN) and ASpartate AminoTransferase (ASAT) levels 2.5 times ULN
15. Inadequate renal function defined by a serum creatinine level more than 1.5 times ULN (alternative: Cockroft less than 50 ml/min)
16. Substances that inhibit CYP3A4 activity, such as rifampicin, phenytoin, ketoconazole, itraconazole

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety: recorded by assessment and documentation in the Case Report Form (CRF) file of adverse events and toxicity (physical examination [with special attention to skin toxicity], laboratory data) at pre-treatment, treatment visits (week one to 12), and follow-up (six months, 12 months).

Secondary Outcome Measures

Name	Time	Method
Efficacy: measured by effects on six minute walk test, stroke volume, changes in High Resolution Computed Tomography (HRCT), N-Terminal B-type Natriuretic Peptide (NT-pro-BNP).