Pulmonary Arterial HypertensionPhase 2PIPAHNCT04416750
Positioning Imatinib for Pulmonary Arterial Hypertension
A Phase 2 study testing Imatinib Mesylate in people with Pulmonary Arterial Hypertension, run by Imperial College London at 4 sites in United Kingdom.
Trial summary
Pulmonary Arterial Hypertension (PAH) is a rare condition in which a narrowing of blood vessels carrying blood through the lungs puts an increased work load on the heart; it has to work harder to pump blood through the lungs. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Imatinib Mesylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- 20 Jan 2021to 1 Jul 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects aged between 18-80 years old
- PAH which is idiopathic; PAH heritable; PAH associated with connective tissue disease; PAH after ≥ 1 year repair of congenital systemic to pulmonary shunt, or PAH associated with anorexigens or other drugs
- Subjects willing to be genotyped for genes that influence PDGF activity
- Resting mean pulmonary artery pressure ≥25 mmHg, Pulmonary capillary wedge pressure ≤15 mmHg, PVR >5 wood units, and normal or reduced cardiac output , as measured by right heart catheterisation (RHC) at entry
- Six-minute walking distance >50m at entry
- Stable on an unchanged PAH therapeutic regime comprising at least 2 therapies licensed for PAH (any combination of endothelin receptor antagonist, phosphodiesterase inhibitor or prostacyclin analogue) for at least 1 month prior to screening
- Able to provide written informed consent prior to any study mandated procedures
- Contraception: Fertile females (women of childbearing potential) are eligible to participate after a negative highly sensitive pregnancy test, if they are taking a highly effective method of contraception during treatment and until the end of relevant systemic exposure. Fertile males who make use of condom and contraception methods during treatment and until the end of relevant systemic exposure in women of childbearing potential -full details are in included in the research protocol-
Who cannot join
- Unable to provide informed consent and/or are non-fluent speakers of the English language
- Hypersensitivity to Imatinib or to any of the excipients
- Clinically-significant renal disease (confirmed by creatinine clearance <30 ml/min per 1.73m2)
- Clinically-significant liver disease (confirmed by serum transaminases >3 times than upper normal limit)
- Patients receiving oral and/or parenteral anticoagulants (this does not apply to single antiplatelet therapy)
- Anaemia confirmed by haemoglobin concentration <10 g/dl
Show all 26Show fewer
- History of thrombocytopenia
- Individuals known to have haemoglobinopathy sickle cell disease, thalassaemia
- Hospital admission related to PAH or change in PAH therapy within 3 months prior to screening
- History of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
- Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency, mild aortic stenosis, mild mitral stenosis, moderate mitral regurgitation
- Mechanical or bioprosthetic cardiac valve
- Pericardial constriction, effusion with tamponade physiology, or abnormal left atrial size.
- Restrictive or congestive cardiomyopathy
- Left ventricular ejection fraction ≤50% (measured in echocardiogram at screening)
- Symptomatic coronary disease
- Significant (2+ for regurgitation) valvular disease other than tricuspid or pulmonary regurgitation
- Acutely decompensated left heart failure within 1 month of screening
- History of untreated obstructive sleep apnoea
- Evidence of significant lung disease on high-resolution CT (if available) or recent (performed within 12 months) lung function, where FEV1 < 50% predicted and FVC < 70% predicted, and DLCO (or TLCO) < 50% predicted if any CT abnormalities; judged by the Site Physician
- Patients with a history of uncontrolled systemic hypertension
- Acute infection (including eye, dental, and skin infections)
- Chronic inflammatory disease including HIV, and Hepatitis B
- Women of childbearing potential who are pregnant or breastfeeding (if applicable)
- Previous intracerebral haemorrhage
- Patients who have received an Investigational Medicinal Product (IMP) within 5 half-lives of the last dose of the IMP or 1 month (whichever is greater) before the baseline visit
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Royal Papworth Hospital, Royal Papworth Hospital NHS Foundation Trust
Cambridge, CB2 0AY
Hammersmith Hospital, Imperial College Healthcare NHS Trust
London, Greater London, W12 0HS
Royal Brompton Hospital, Royal Brompton & Harefield NHS Foundation Trust
London, SW3 6NP
Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation
Sheffield, S10 2JF
About this study
Pulmonary Arterial Hypertension (PAH) is a rare condition in which a narrowing of blood vessels carrying blood through the lungs puts an increased work load on the heart; it has to work harder to pump blood through the lungs. While current treatments relieve some of the symptoms, they do not stop or reverse the disease in the affected blood vessels. Imatinib is a medicine licensed for some types of cancers. A published study has shown that imatinib can have beneficial effects on blood flow through the lungs and exercise capacity in patients with PAH, even when added to existing treatments. However, there have been concerns about its safety and tolerability. Imatinib continues to be prescribed occasionally on compassionate grounds, usually when other treatment options have been exhausted, and some patients feel better on the drug. To improve the investigator's understanding, the investigators of this study re-visits the use of Imatinib as a potential treatment for patients with PAH.
Read the detailed description
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
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Imatinib Mesylate
- Keywords
- Pulmonary Arterial Hypertension, PAH, Imatinib, TKI, Genotype
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib MesylateDrug
Also called Oral treatment
Treatment with Imatinib
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Open label; Imatinib tablets administered once daily; Dosage: in the range of 100mg-400mg; Group evaluated: adults with PAH Receives: Drug: Imatinib Mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identifying the highest tolerated dose
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.
Measured: 12 months
Change in pulmonary vascular resistance (PVR)
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.
Measured: 24 months
Secondary outcomes (4)
Change in exercise test
Change in six minute walk distance (6MWD) at 24 weeks.
Measured: 24 weeks
Change in ejection fraction measures
Change in right ventricular ejection fraction (RVEF) values, measured in echocardiogram (at screening visit and at 24 weeks).
Measured: 24 weeks
Change in brain natriuretic peptide (BNP) values
Change in plasma BNP (or proNT-BNP) levels from baseline at 24 weeks.
Measured: 24 weeks
Change in quality of life scores
Change in Quality of Life (QoL) scores from baseline at 24 weeks.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start20 Jan 2021
- Primary completion1 Jul 2024 (estimated)
- Study completion1 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The highest tolerated dose of Imatinib determined using a Bayesian continual reassessment method. In the first part, 13 patients were recruited sequentially by protocol at a minimum of 4 week intervals. Each patient was administered a dose of imatinib between 100mg and 400mg daily. The selected dose for each patient was based upon the safety and tolerability of doses administered to preceding recruits using a Bayesian continuous reassessment method. The inclusion of patients with implanted monitoring devices allowed us to collect data on an early efficacy marker alongside data on safety and tolerability. With a small extension, we gained further data on the effect of imatinib on cardiopulmonary haemodynamics and activity in PAH patients, covering the full 100mg to 400mg dose range.
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Medical Research Council, University of Cambridge, University of Sheffield
- Responsible party
- Sponsor
- Investigators
- Martin R Wilkins, MD, FRCP, Study director, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04416750
- Sponsor's protocol ID
- IRAS ID: 274093
- Other IDs
- 2020-001157-48, 20HH5896, 20/SC/0240
- Acronym
- PIPAH
- Status last verified
- Oct 2023
- First submitted
- 28 May 2020
- Last updated
- 10 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Positioning Imatinib for Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT04416750
- Acronym / sponsor ID
- PIPAH / IRAS ID: 274093
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- Pulmonary Arterial Hypertension, PAH, Imatinib, TKI, Genotype
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Medical Research Council, University of Cambridge, University of Sheffield
- Study start
- 20 Jan 2021 (actual)
- Primary completion
- 1 Jul 2024 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 4 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pulmonary Arterial Hypertension (PAH) is a rare condition in which a narrowing of blood vessels carrying blood through the lungs puts an increased work load on the heart; it has to work harder to pump blood through the lungs. While current treatments relieve some of the symptoms, they do not stop or reverse the disease in the affected blood vessels. Imatinib is a medicine licensed for some types of cancers. A published study has shown that imatinib can have beneficial effects on blood flow through the lungs and exercise capacity in patients with PAH, even when added to existing treatments. However, there have been concerns about its safety and tolerability. Imatinib continues to be prescribed occasionally on compassionate grounds, usually when other treatment options have been exhausted, and some patients feel better on the drug. To improve the investigator's understanding, the investigators of this study re-visits the use of Imatinib as a potential treatment for patients with PAH.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The highest tolerated dose of Imatinib determined using a Bayesian continual reassessment method. In the first part, 13 patients were recruited sequentially by protocol at a minimum of 4 week intervals. Each patient was administered a dose of imatinib between 100mg and 400mg daily. The selected dose for each patient was based upon the safety and tolerability of doses administered to preceding recruits using a Bayesian continuous reassessment method. The inclusion of patients with implanted monitoring devices allowed us to collect data on an early efficacy marker alongside data on safety and tolerability. With a small extension, we gained further data on the effect of imatinib on cardiopulmonary haemodynamics and activity in PAH patients, covering the full 100mg to 400mg dose range.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Imatinib MesylateOpen label; Imatinib tablets administered once daily; Dosage: in the range of 100mg-400mg; Group evaluated: adults with PAH |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subjects aged between 18-80 years old
- PAH which is idiopathic; PAH heritable; PAH associated with connective tissue disease; PAH after ≥ 1 year repair of congenital systemic to pulmonary shunt, or PAH associated with anorexigens or other drugs
- Subjects willing to be genotyped for genes that influence PDGF activity
- Resting mean pulmonary artery pressure ≥25 mmHg, Pulmonary capillary wedge pressure ≤15 mmHg, PVR >5 wood units, and normal or reduced cardiac output , as measured by right heart catheterisation (RHC) at entry
- Six-minute walking distance >50m at entry
Key exclusion criteria (26 listed)
- Unable to provide informed consent and/or are non-fluent speakers of the English language
- Hypersensitivity to Imatinib or to any of the excipients
- Clinically-significant renal disease (confirmed by creatinine clearance <30 ml/min per 1.73m2)
- Clinically-significant liver disease (confirmed by serum transaminases >3 times than upper normal limit)
- Patients receiving oral and/or parenteral anticoagulants (this does not apply to single antiplatelet therapy)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imatinib MesylateAlso: Oral treatmentTreatment with Imatinib | Drug | Treatment |
Primary outcome
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.
4 secondary outcomes
Change in exercise test
Time frame: 24 weeks
Change in ejection fraction measures
Time frame: 24 weeks
Change in brain natriuretic peptide (BNP) values
Time frame: 24 weeks
Change in quality of life scores
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
Related trials for Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Recruiting
Trial to Evaluate Safety And Effectiveness of Mechanical Circulatory Support in Patients With Advancing Heart Failure
Heart Failure, Heart Diseases
RecruitingPhase 4
Sotatercept in Pulmonary Arterial Hypertension
Pulmonary Artery Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
RecruitingPhase 2/3
The Effect of Additive On-Demand Sildenafil vs. Dextrose Candy on Maximum Exercise Capacity in Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin R Wilkins, MD, FRCP study director
Imperial College London
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib Mesylate in people with Pulmonary Arterial Hypertension, run by Imperial College London at 4 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identifying the highest tolerated dose (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2023.