AuthorisedTherapeutic exploratory (Phase II)Interventional

DIRECTION- Discontinuation versus continuation of riociguat monotherapy in chronic thromboembolic pulmonary hypertension successfully treated with balloon pulmonary angioplasty

Chronic thromboembolic pulmonary hypertension (CTEPH) is high blood pressure in the lungs caused by old blood clots. Many people with CTEPH take a daily tablet called riociguat to relax lung blood vessels and improve blood flow. Many also have a procedure called balloon pulmonary angioplasty (BPA), which uses tiny balloons to open narrowed arteries in the lungs. After a successful balloon procedure, it is unclear whether patients still need riociguat. Stopping medicine that is no longer needed could save patients from side effects and reduce healthcare costs. However, stopping it might also cause symptoms to return. The DIRECTION trial compares patients who stop taking riociguat with those who continue taking it. Doctors will check participants regularly for at least one year to monitor walking ability, heart pressure, and general quality of life to see which approach is safest.

At a glance

Status

Authorised

Phase

Therapeutic exploratory (Phase II)

Sponsor

Assistance Publique Hopitaux De Paris

Enrolment target

150

Start

25 Aug 2026

chronic thromboembolic pulmonary hypertension

What is this study about?

Chronic thromboembolic pulmonary hypertension (CTEPH) happens when past blood clots leave scars that narrow or block the blood vessels in your lungs. This raises blood pressure in the lungs and puts extra strain on the right side of the heart, leaving people short of breath and tired. Doctors often treat this condition with a medicine called riociguat, which widens lung blood vessels, and with a procedure called balloon pulmonary angioplasty (BPA), which clears blockages using tiny balloons.

When a balloon procedure works well, blood flow through the lungs improves significantly. This raises an important question for specialists: do patients still need to take riociguat every day once the blood vessels have been opened mechanically? Taking long-term tablets can cause side effects, requires regular check-ups, and places a cost on health services. At the same time, doctors must be certain that stopping the medicine will not cause blood pressure in the lungs to rise again.

This clinical trial, named DIRECTION, aims to give a clear answer. Half of the participants will carry on taking riociguat, while the other half will carefully stop taking it. Both groups will be followed closely by specialist hospital teams. By comparing how both groups do over time, the study will help doctors worldwide decide the safest and best treatment plan for people who have recovered well after balloon procedures.

Key takeaways

The trial tests whether it is safe to stop riociguat after successful balloon treatment for CTEPH.
Participants either carry on taking riociguat or stop taking it under close medical watch.
You will be monitored for at least 12 months with walking tests, blood tests, and heart checks.
If your health worsens at any point, your care team can restart your medication immediately.
Participation is entirely voluntary and you can change your mind at any point.

Who may be eligible?

This trial is for adults aged 18 or older who have been diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH).

To be eligible, you must have already had successful balloon pulmonary angioplasty (BPA) treatment to widen your lung blood vessels, and you must currently be taking riociguat as your only specific medicine for pulmonary hypertension.

You may not be able to join if you take other specific pulmonary hypertension tablets alongside riociguat, if your balloon procedure was not successful, or if your medical team feels your condition is not stable enough to consider altering your medication.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 18 or over.
I have been diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH).
I have had a successful balloon pulmonary angioplasty (BPA) procedure.
I am currently taking riociguat as my only pulmonary hypertension tablet.
My health is stable following my balloon procedure.

Answer every question to see your result.

What does participation involve?

If you take part, you will be placed into one of two groups: one group continues taking their riociguat tablets as usual, while the other group gradually stops taking them. You will take part for at least 12 months, and possibly longer until the study finishes.

You will attend regular hospital appointments at the start, at months 3, 6, and 12, and then every 6 months after that. At these visits, doctors will measure how far you can walk in six minutes, check your general breathing, take routine blood samples, and ask you to complete short questionnaires about your daily life. At the start and after one year, you will also have tests to check the blood pressure inside your heart and lungs. If your symptoms worsen at any stage, your medical team will step in promptly to adjust your care.

Potential risks and benefits

A potential benefit of joining is having very regular, detailed check-ups by lung and heart specialists, which ensures any changes in your health are spotted early. If you stop the medication safely, you may avoid daily tablet-taking and related side effects. The main risk is that stopping riociguat might cause your breathing symptoms or lung blood pressure to worsen. There is also minor discomfort from blood tests and heart monitoring. Taking part is completely voluntary, and you can leave the study and restart your usual medication at any time without your normal NHS care being affected.

Locations (1)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

—
Unverified
France

Common questions

What is riociguat?

Riociguat is a daily tablet that helps relax and widen the blood vessels in your lungs, making it easier for your heart to pump blood through them.

What is balloon pulmonary angioplasty (BPA)?

BPA is a hospital procedure where a doctor passes a tiny balloon through a thin tube into your lungs. The balloon is inflated to gently stretch open arteries narrowed by old clots.

Will I definitely have to stop taking my medication?

Not necessarily. A computer system randomly decides whether you continue taking riociguat or stop it, ensuring a fair scientific comparison between the two groups.

What happens if my breathing gets worse after stopping riociguat?

Your safety comes first. The medical team will check you closely, and if your condition worsens, they can restart your medicine or offer other proven treatments straight away.

Do I have to pay to take part?

No, all study-related visits, health checks, and trial procedures are provided at no cost to you.