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

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN75611179
• Date of registration: 01/02/2007
• Prospective Registration: No
• Primary sponsor: VU University Medical Centre (The Netherlands)
• Public title: The effects of epidermal growth factor receptor inhibition on pulmonary arterial hypertension associated with systemic sclerosis
• Date of first enrolment: 01/01/2007
• Target sample size: 20
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN75611179
• Study type: Interventional
• Study design: Phase II study, open-labelled trial (Treatment)

Countries of recruitment

Netherlands

Contacts

• Name: A Boonstra

Key inclusion & exclusion criteria

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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

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

Intervention(s)

All participants will receive cetuximab at a loading dose of 400 mg/m^2 in week one, followed by a weekly dose of 250 mg/m^2 starting from week two, up to a total of 12 weeks.

Primary Outcome(s)

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(s)

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).

Secondary ID(s)

155/2006

Source(s) of Monetary Support

VU University Medical Center (The Netherlands)