Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04416750|
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : September 20, 2021
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Arterial Hypertension||Drug: Imatinib Mesylate||Phase 2|
What does the study involve?
The study involves treatment of PAH patients with imatinib (study drug) for up to 24 weeks, and clinical assessments and tests to assess the drug's safety and tolerability.
PAH patients will be seen at their local hospital by the PAH clinical research team. Before someone can start study, the study doctor (or clinical study team) will describe the clinical trial in detail. If a potential subject decides to participate, he/she will be asked to sign the informed consent form before any study procedures are done.
Participants will be asked to come to their local hospital for clinical appointments. This includes a screening visit, a baseline visit, three clinical assessments and an end-of-study visit. In between, and at the very end of these, there will be six tele-visits (assessments over the phone). Each clinical appointment will be on a weekday morning or afternoon. No major lifestyle restrictions are required for these appointments.
Participants will undergo clinical examinations and tests to monitor the severity of PAH and the response to the study drug. Clinical procedures include:
- Questions about demographics, medical and medication history
- Physical examination and record of vital signs (blood pressure, temperature, heart and respiratory rate)
- Questionnaire about quality of life,
- Assessments of PAH severity (WHO Functional Class, six-minute walk test, and Borg dyspnoea index)
- Right heart catheterisation to assess response to the drug
- Haematology and clinical chemistry blood tests to ensure safety
- Serum pregnancy test and urine pregnancy tests (if applicable) to exclude pregnancy
- Blood samples to measure the levels of the study drug in the circulation
- Additional blood samples for future research on PAH and/or the mechanism of action of the drug
- Electrocardiogram (ECG), and echocardiogram to assess the size, shape, pumping action and the extent of any damage to the heart
- Brain MRI scan (or CT scan if MR is not indicated/tolerated) to exclude bleeding in the brain
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||The highest tolerated dose of Imatinib will be determined using a Bayesian continual reassessment method. Treatment efficacy at the pre-determined highest tolerated dose will be assessed using a Simons two stage design.|
|Masking:||None (Open Label)|
|Official Title:||Positioning Imatinib for Pulmonary Arterial Hypertension|
|Actual Study Start Date :||January 20, 2021|
|Estimated Primary Completion Date :||July 1, 2024|
|Estimated Study Completion Date :||July 1, 2024|
Open label; Imatinib tablets administered once daily; Dosage: in the range of 100mg-400mg; Group evaluated: adults with PAH
Drug: Imatinib Mesylate
Treatment with Imatinib
Other Name: Oral treatment
- Identifying the highest tolerated dose [ Time Frame: 12 months ]Part 1: Discontinuation of the drug for more than 5 consecutive days due to Grade 2 or above Adverse Events, defined by NCI criteria (version 5.0, 2017) adapted for the study.
- Change in pulmonary vascular resistance (PVR) [ Time Frame: 24 months ]Part 2: The primary efficacy endpoint is a binary variable. For patients with a baseline pulmonary vascular resistance (PVR) >1000 dynes·s·cm-5, success is defined by an absolute reduction in PVR of ≥300 dynes·s·cm-5 at 24 weeks. For patients with a baseline PVR ≤1000 dynes·s·cm-5, success is a 30% reduction in PVR at 24 weeks.
- Change in exercise test [ Time Frame: 24 weeks ]Change in six minute walk distance (6MWD) at 24 weeks.
- Change in ejection fraction measures [ Time Frame: 24 weeks ]Change in right ventricular ejection fraction (RVEF) values, measured in echocardiogram (at screening visit and at 24 weeks).
- Change in brain natriuretic peptide (BNP) values [ Time Frame: 24 weeks ]Change in plasma BNP (or proNT-BNP) levels from baseline at 24 weeks.
- Change in quality of life scores [ Time Frame: 24 weeks ]Change in Quality of Life (QoL) scores from baseline at 24 weeks.
- Plasma proteome measures [ Time Frame: 24 weeks ]Change in plasma proteome from baseline at 24 weeks.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04416750
|Contact: Andreas-Antonios Roussakis, MD, PhD||+44(0)firstname.lastname@example.org|
|Hammersmith Hospital, Imperial College Healthcare NHS Trust||Recruiting|
|London, Greater London, United Kingdom, W12 0HS|
|Contact: Luke Howard, Dr|
|Sub-Investigator: Gulammehdi Haji, Dr|
|Royal United Hospital, Royal United Hospitals Bath NHS Foundation Trust||Not yet recruiting|
|Bath, United Kingdom, BA1 3NG|
|Contact: Jay Suntharalingam, Dr|
|Royal Papworth Hospital, Royal Papworth Hospital NHS Foundation Trust||Not yet recruiting|
|Cambridge, United Kingdom, CB2 0AY|
|Contact: Mark Toshner, Dr|
|Golden Jubilee National Hospital, NHS Greater Glasgow and Clyde||Not yet recruiting|
|Glasgow, United Kingdom, G81 4DY|
|Contact: Colin Church, Dr|
|Royal Free Hospital, Royal Free London NHS Foundation Trust||Not yet recruiting|
|London, United Kingdom, NW3 2QG|
|Contact: Gerry Coghlan, Dr|
|Royal Brompton Hospital, Royal Brompton & Harefield NHS Foundation Trust||Not yet recruiting|
|London, United Kingdom, SW3 6NP|
|Contact: John S Wort, Dr|
|Newcastle Freeman Hospital, The Newcastle Upon Tyne Hospitals NHS Foundation Trust||Not yet recruiting|
|Newcastle Upon Tyne, United Kingdom, NE7 7DN|
|Contact: Jim Lordan, Dr|
|Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation||Recruiting|
|Sheffield, United Kingdom, S10 2JF|
|Contact: Alexander Rothman, Dr|
|Sub-Investigator: David Kiely, Prof|
|Sub-Investigator: Robin Condliffe, Dr|
|Study Director:||Martin R Wilkins, MD, FRCP||Imperial College London|