Riociguat in patients with respiratory disease and hypoxia
| ISRCTN | ISRCTN60323736 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN60323736 |
| EudraCT/CTIS number | 2014-001008-23 |
| Secondary identifying numbers | 17131 |
- Submission date
- 11/03/2015
- Registration date
- 11/03/2015
- Last edited
- 07/05/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
This is a proof-of-concept study (i.e. a study to test a concept or theory to see whether it can work) to establish the effects of a drug called Riociguat in patients with lung disease. Pulmonary hypertension is a serious health condition in which the blood pressure in the vessels supplying the lungs (pulmonary arteries) is too high. Over time, this can lead to damage to the right hand side of the heart, which can affect how well it functions. Symptoms of the condition include breathlessness, tiredness, chest pains, palpitations and leg/ankle swelling. Riociguat is a new drug which was recently been approved for the treatment of two forms of pulmonary hypertension: pulmonary arterial hypertension and pulmonary hypertension that arises as a result of persistent blood clots in the lung vessels. Pulmonary hypertension can also arise in patients with lung disease who have low oxygen levels (hypoxia). Treatment options are limited and the outcome for these patients is poor so new treatment approaches are needed. We therefore wish to conduct a pilot study to establish the effects of Riociguat on symptoms, oxygen levels and right heart function in patients with lung disease who have reduced oxygen levels.
Who can participate?
Adults aged 40-80 diagnosed with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis (IPF).
What does the study involve?
Prior to participants taking the study drug, they undergo an initial right heart catheterisation (a test to measure heart function and the pressures in the heart and lungs) and oxygen flight assessment test (a test to see whether they can fly at altitude without needing a supply of oxygen). Participants are then started on Riociguat. They are initially given a 1mg dose, three times a day. This is slowly increased every two weeks up until a maximum dose of 2.5mg, three times a day. Participants then undergo another right heart catheterisation and oxygen flight assessment test. Once these are done, the study medication is discontinued.
What are the possible benefits and risks of participating?
Due to the nature of the study being proof-of-concept, there will be no direct benefits to the participants but it is hoped that any findings could prompt further large scale studies in this area. The only risks involved in this study relate to the study interventions, namely right heart catheterisation and taking the study medication, Riociguat. Right heart catheterisation is a routine procedure performed in our centre and the frequency of any risk such as pain, bleeding or abnormal heart rhythms is less than 1%. The amount of radiation used during the procedure in the form of X-ray guidance equates to no more than three times the amount of normal background radiation exposure in one year. Previous trials of Riociguat have shown most of the side effects are non-severe and relate to either dizziness (from reduced blood pressure) or gastro-intestinal symptoms. The only serious problem that has occurred in previous studies is coughing up blood, but less than 1% of participants have experienced this.
Where is the study run from?
Freeman Hospital (UK)
When is the study starting and how long is it expected to run for?
December 2014 to May 2015
Who is funding the study?
Bayer Healthcare (Germany)
Who is the main contact?
Dr Logan Thirugnanasothy
Contact information
Scientific
Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Study information
| Study design | Non-randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Riociguat in patients with respiratory disease and hypoxia – a proof-of-concept study |
| Study acronym | RIOPRED |
| Study objectives | Our hypothesis is that Riociguat at a maximum tolerated dose will prevent changes in oxygen saturation, pulmonary vascular resistance and mean pulmonary artery pressure (PAP) that are precipitated by worsening hypoxia in patients with respiratory disease. |
| Ethics approval(s) | NRES Committee North East - Newcastle & North Tyneside 2, 16/07/2014, ref: 14/NE1057 |
| Health condition(s) or problem(s) studied | Topic: Respiratory disorders; Subtopic: Respiratory (all Subtopics); Disease: Respiratory |
| Intervention | Participants will initially undergo right heart catheterisation which measures right heart function and pressure. This is followed by a hypoxic challenge test which is used in routine clinical practice to determine if certain respiratory patients require oxygen for air travel. The right heart function and pressure measurements are then repeated. Participants will then be given the study drug, Riociguat. The study drug will be started initially at 1mg, three times daily and titrated fortnightly according to blood pressure, with a maximum possible dose of 2.5mg, three times daily. When the participant is on the maximum tolerated dose, participants will undergo repeat right heart catheterisation and hypoxic challenge testing. Other assessments that will be performed for secondary outcome measures will be oxygen saturations, severity of breathlessness and lung function testing. The following assessments will then be undertaken. 1. Spirometry and diffusing capacity: routine breathing tests to measure lung function 2. Venepuncture: bloods samples will be updated to ensure eligibility for the study and will be repeated as part of the drug safety monitoring process. 3. Right heart catheterisation: the diagnostic procedure performed for suspected pulmonary hypertension where the function and pressure in the right heart is measured. 4. Hypoxic challenge test: a gas mixture of 15% Oxygen is inhaled for up to 20 minutes. 5. Arterial blood gas: a blood test to measure the levels of oxygen and carbon dioxide. 6. Riociguat: the study drug will be started initially at 1mg, three times daily and titrated fortnightly according to blood pressure, with a maximum possible dose of 2.5mg, three times daily. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Riociguat |
| Primary outcome measure | The acute effects of Riociguat on: 1. Oxygen saturations (SaO2) 2. The partial pressure of oxygen (PaO2) 3. Mean pulmonary artery pressure (PAP) 4. Pulmonary vascular resistance (PVR) 5. Perceived breathlessness The information will be recorded at both episodes of right heart catheterisation/hypoxic challenge test. Measurement tools: 1. Pulse oximeter 2. Arterial blood gas 3. Right Heart Catheterisation 4. Visual analogue scale for breathlessness 5. Pulmonary function test |
| Secondary outcome measures | The effects of Riociguat on diffusing capacity, SaO2 and on perceived breathlessness, along with safety in respiratory patients, recorded from the screening/consent visit and the final visit of drug titration. |
| Overall study start date | 17/06/2014 |
| Completion date | 31/08/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 10; UK Sample Size: 10 |
| Total final enrolment | 10 |
| Key inclusion criteria | 1. Age 40 to 80 years, Male and Female 2. Primary diagnosis of either chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) with recent stability 3.Capacity and willingness to provide fully informed consent for participation in the study |
| Key exclusion criteria | 1. On prescribed oxygen therapy, nitrates (tablets or sublingual), dipyridamole, theophylline, warfarin, clopidogrel, rivaroxaban and dabigatran 2. Other concomitant respiratory diagnoses including asthma, interstitial lung disease (not idiopathic), pulmonary hypertension (of any other aetiology), lung cancer, recent respiratory infection, recent acute pulmonary embolism, recent pneumothora 3. Unable to give written, informed consent •Contraindication to spirometry not included elsewhere: recent eye surgery, glaucoma 4. Uncontrolled arterial hypertension (systolic BP > 180mmHg and/or diastolic BP > 110mmHg 5. Systolic BP < 95mmHg 6. Resting awake heart rate < 50 beats per minute or > 105bpm 7. History of uncontrolled atrial fibrillation within 3 months of screening 8. Left heart failure with an ejection fraction less than 40% 9. Hypertrophic Obstructive Cardiomyopathy (HOCM) 10. Proven or suspected active or recent* coronary artery disease 11. Other active atherosclerotic disease: active peripheral arterial disease, stroke within 3 months of screening 12. Significant valvular heart disease 13. History of active or serious haemoptysis/pulmonary haemorrhage 14. Hepatic dysfunction 15. Bilirubin > 2 times ULN at screening and/or 16. ALT or AST > 3 times ULN at screening and/or 17. Albumin < 32g/L/hepatic encephalopathy > grade 1 at screening 18. Renal insufficiency: GFR < 30ml/min 19. Pregnant or lactating women |
| Date of first enrolment | 17/12/2014 |
| Date of final enrolment | 30/06/2016 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Sponsor information
Hospital/treatment centre
Wolfson Unit of Clinical Pharmacology
Institute of Cellular Medicine
Framlington Place
Newcastle Upon Tyne
NE2 4HH
England
United Kingdom
"ROR" |
https://ror.org/05p40t847 |
|---|
Funders
Funder type
Government
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- BHC
- Location
- Germany
Results and Publications
| Intention to publish date | 31/08/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Plans for publication will be in 2016 in a peer reviewed journal, along with presentation at relevant Pulmonary Hypertension meetings. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | 08/11/2016 | 07/05/2021 | No | No |
Editorial Notes
07/05/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
08/12/2016: The overall trial end date has been updated from 31/12/2015 to 31/08/2016 and the recruitment end date has been updated from 17/05/2015 to 30/06/2016.
