Investigating the effect of a medication on the blood pressure within the lungs

Plain English summary of protocol

Background and study aims
The blood vessels within the lungs are unique. In other parts of the body, when there is not enough oxygen present, the blood vessels increase in size (dilate) to deliver more blood to the organs. However, in the lungs, they narrow (constrict; causing an increase in blood pressure) and we can see this using ultrasound of the heart.
These blood vessels can constrict more effectively under certain circumstances. For example, we know that when a lack of oxygen (termed hypoxia) continues for several hours, the blood vessels are able to react more strongly. This means the blood pressure in the lungs increases to a higher level. This happens because a ‘signalling pathway’ is activated – a cascade of steps that results in genes being switched on from our DNA.
A drug called roxadustat deliberately switches on this pathway. It is licensed in many countries, including the UK, to treat the anaemia (low haemoglobin and red blood count) that accompanies long-term kidney disease. This is a good thing, and the drug has been shown to be safe. However, we don't yet know what this drug does to the blood vessels in the lungs in hypoxia. Based on what we know already, we would expect that it would make them react more strongly. This is important as many people around the world will be taking this drug for a long time.
Therefore, the aim of this study is to give a single one-off dose of roxadustat to healthy volunteers and measure the blood pressure in the lungs (using ultrasound) when they are breathing normal air, and when they are breathing in less oxygen. This will tell us what effect the drug is having on the blood vessels in the lungs, and help guide scientists and doctors in the future.

Who can participate?
Healthy volunteers aged 19–60 years

What does the study involve?
At the preliminary visit participants undergo a heart ultrasound check and blood test to make sure they are able to take part. On the first study day they are randomly allocated to take either roxadustat or a placebo (sugar) tablet, and also undergo heart ultrasounds and breathe low oxygen for 30 minutes (with a mouthpiece and nose clip) for 2 hours in a comfortable, purpose-built ‘chamber’ – a small room with windows. On the second study day (at least 2 weeks later) participants undergo exactly the same steps as the first experiment day. but they take the opposite tablet to the one taken on the first study date (i.e. if they took roxadustat on Day 1 they take the placebo on Day 2, and vice versa).

What are the possible benefits and risks of participating?
While there are no immediate benefits for those people participating in the project, it is hoped that this study will lead to a better understanding of the science of hypoxia and the blood pressure in the lungs, as well as important safety information for patients taking roxadustat.

Risk 1 - Hypoxia:
Participants will be exposed to hypoxia as per the study protocol and under identical conditions to multiple studies conducted in the same laboratory. The lowest end-tidal PO2 will be 50 mmHg (equivalent to ascent to an altitude of about 3000 – 5000 m) and this is a well-established experimental technique that produces robust physiological changes without risk to the individual. The participant may notice increased work of breathing, which is a normal physiological response. Safety mechanisms are built into the experimental equipment and these have been rigorously tested over many years of approved research studies.

Risk 2 - Roxadustat:
This is a well-established and fully licensed drug that has gone through all the required clinical trials. It is now recommended by NICE as a treatment option for symptomatic anaemia associated with chronic kidney disease. Roxadustat treatment is known to produce a dose-dependent increase in heart rate in healthy subjects at doses over 2 mg/kg (applicable for this study) but with no adverse events reported (EMA report). Participants will be informed that a small increase in heart is to be expected, and reassured that it is normal and safe. The safety of roxadustat was evaluated in 3542 non-dialysis-dependent (NDD) and 3353 dialysis-dependent (DD) patients with anaemia and chronic kidney disease who have received at least one dose of roxadustat. The most frequent (≥10%) adverse reactions associated with roxadustat are hypertension (13.9%), vascular access thrombosis (12.8%), diarrhoea (11.8%), peripheral oedema (11.7%), hyperkalaemia (10.9%) and nausea (10.2%). The most frequent (≥1%) serious adverse reactions associated with roxadustat were sepsis (3.4%), hyperkalaemia (2.5%), hypertension (1.4%) and deep vein thrombosis (1.2%).

It should be noted, however, that these adverse events were reported from patients with chronic kidney disease on sustained dosing, and are therefore less applicable to individual healthy participants receiving a single one-off dose. A large number of healthy volunteers underwent Phase I trials and there are no reported adverse events in the literature by the reviewing authorities.

Where is the study run from?
University of Oxford (UK)

When is the study starting and how long is it expected to run for?
January 2023 to December 2025

Who is funding the study?
Medical Research Council (MRC) (UK)

Who is the main contact?
Dr Mary Slingo, mary.slingo@dpag.ox.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• United Kingdom
• England

Study participating centre

Results and Publications

Study outputs

Editorial Notes

30/10/2025: The date of final enrolment was changed from 31/12/2025 to 13/05/2025.
20/02/2025: The study record was confirmed as being up to date.
14/12/2023: Study's existence confirmed by the medical sciences interdivisional research ethics committee, CUREC 3.