A randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of six months treatment with the tyrosine kinase inhibitor of STI571 for the treatment of pulmonary arterial hypertension.

• Register: EUCTR
• Last refreshed on: 5 August 2014
• Main ID: EUCTR2005-005569-12-DE
• Date of registration: 27/03/2006
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of six months treatment with the tyrosine kinase inhibitor of STI571 for the treatment of pulmonary arterial hypertension.
• Scientific title: A randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of six months treatment with the tyrosine kinase inhibitor of STI571 for the treatment of pulmonary arterial hypertension.
• Date of first enrolment: 24/05/2006
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005569-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Germany, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female patients equal to or greater than 18 years of age.
2. Diagnosis of pulmonary arterial hypertension (PAH) according to the Venice classification system (2003), of either primary (idiopathic), familial or secondary to systemic sclerosis (excluding those with marked pulmonary fibrosis).
3. Female patients of child bearing potential must be using a double-barrier contraception, i.e. intra-uterine device plus condom, or spermicidal gel plus condom or oral contraceptive plus condom up to completion of the Study Completion visit.
4. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.
5. Subjects who are presently receiving imatinib following participation in the randomized STI571E2203 Study or subjects who will complete participation in the six month randomized STI571E2203 Study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Any subject who did not participate in the STI571E2203 Study.
2. Any subject who experienced syncope, pre syncope or new arrhythmias while participating in the STI571E2203.
3. Donation or loss of 400 ml or more of blood within 8 weeks prior to participation in the extension study.
4. Any subject who has developed any of the following exclusion criteria during participation in the STI571E2203 Study (subjects who are already receiving compassionate use imatinib, but have developed any of the following will be considered on a case by case basis).
- Chronic thromboembolic pulmonary hypertension.
- Treatment with catecholamines (e.g. adrenalin > 500 ng/kg x min, noradrenalin > 500 ng/kg x min, dopamine > 5 ng/kg x min).
- Acute heart failure or chronic left sided heart failure.
- Severe (systemic) arterial hypertension (> 200 mmHg (systolic) or > 120 mmHg (diastolic).
- Congenital or acquired valvular or myocardial disease.
- Deficiencies of blood coagulation (i.e. based on relevant changes in coagulation parameters), inherited or acquired blood coagulation disorders e.g. defects in factor VIII (Haemophilia A, v. Willebarnd syndrome), factor XII, factor XIII;decreased generation of coagulation factors due to acute or chronic liver diseases, deficient coagulation due to auto-antibodies against coagulation factors such as in lupus anticoagulant.
- Disseminated intravascular coagulation (DIC).
- Deficient thrombocyte function, thrombocytopenia < 40000/µl.
- Evidence of major bleeding or intracranial hemorrhage.
- History of latent bleeding risk such as diabetic retinopathy, history of gastrointestinal bleeding (due to gastric or duodenal ulcers), or colitis ulcerosa.
- Moderate hepatic insufficiency Transaminase levels >= 4 fold the upper limit of normal or a bilirubin >= 2 fold the upper limit of normal. Elevated transaminase level should be carefully monitored because of known liver toxicity of STI571.
- Renal insufficiency (serum creatinine > 200 µmol/l).
- Previous therapeutic radiation of lungs or mediastinum.
- History of elevated intracranial pressure (ICP >= 20 mmHg).
- Pregnancy, breast feeding.
- Patients whose underlying disease is not likely to permit them to survive the study.
- Sickle cell anemia.
- History of drug or alcohol abuse within the 12 months prior to dosing.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

pulmonary arterial hypertension

Intervention(s)

Trade Name: Glivec 100 mg Hartkapsel
Product Name: Glivec
Product Code: STI571
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Imatinib
CAS Number: 152459-95-5
Current Sponsor code: STI571
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Glivec 100 mg Filmtabletten
Product Name: Glivec
Product Code: STI571
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Imatinib
CAS Number: 152459-95-5
Current Sponsor code: STI571
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: • To assess the safety and tolerability of oral STI571 compared with placebo in patients with pulmonary arterial hypertension.
• To evaluate efficacy of oral STI571 as measured by improvement in 6-minute walk test.

Primary end point(s): The primary efficacy analysis, will be on the difference between six minute walk tests at Week 24 between the two treatment groups, appropriate statistical testing will be performed on an intention to treat basis. A secondary analysis on the per protocol population will also be performed.
Further analysis will be performed on all other secondary variables, where the mean and confidence interval for each variable will be listed and appropriate statistical comparisons made.

Secondary Objective: •To evaluate the efficacy of oral STI571 as measured by improvement Borg dyspoena scale, clinical status (WHO/NYHA class and dyspoena score), and changes in pulmonary haemodynamic parameters (including mean pulmonary arterial pressure, cardiac output and pulmonary vascular resistance) time to clinical worsening, changes in plasma biomarker levels.
•To collect and monitor safety data of imatinib, provided as open label medication to patients with pulmonary arterial hypertension (PAH) who were enrolled in the six month randomized, placebo controlled STI571E2203 study.

Secondary ID(s)

2005-005569-12-GB

CSTI571E2203