Discontinuing vs Continuing Riociguat in Chronic Thromboembolic Pulmonary Hypertension Patients After Successful Balloon Pulmonary Angioplasty

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What is this study about?

The investigation focuses on chronic thromboembolic pulmonary hypertension, a condition where blood clots cause high pressure in the lungs’ arteries, leading to strain on the heart. Participants have previously undergone balloon pulmonary angioplasty, a procedure that uses a small balloon to open narrowed lung vessels, and are being treated with the oral medication riociguat. The purpose of the study is to estimate the risk of clinical worsening when the drug is stopped compared with continuing it after a successful angioplasty.

After successful angioplasty, eligible individuals are divided into two groups: one continues taking riociguat and the other stops the medication. Both groups are followed for at least twelve months, with regular clinic visits to monitor health status. Simple tests include a walking test that measures how far a person can walk in six minutes (6‑minute walk distance) and questionnaires that assess daily functioning and quality of life, such as the EQ-5D-5L and disease‑specific EmPHasis‑10. Blood tests for a heart‑stress marker (NT-proBNP) and routine checks of heart function are also performed.

During the follow‑up period, any serious events such as death, hospitalization because of worsening lung pressure, right heart failure, need for a lung transplant, use of intravenous diuretics or inotropic support, or requirement of medication called prostanoids are recorded. The study aims to provide information on whether stopping riociguat after a successful procedure is safe or if continuing the medication offers better protection against these serious outcomes.

1 initial study visit

after joining the study, you will meet the study team and give written consent to take part.

you will undergo baseline measurements that include the 6‑minute walk distance, assessment of who functional class (a rating of symptom severity), a blood test for nt‑probnp (a marker of heart strain), and questionnaires that evaluate quality of life (eq‑5d‑5l and emphasis‑10).

additional heart pressure measurements may be performed to record your condition before treatment.

2 start riociguat medication

you will receive tablets of riociguat with a dose of 7.5 mg.

the medication is taken by mouth as instructed by the study team and is continued daily until the study directs otherwise.

3 balloon pulmonary angioplasty procedure

you will undergo balloon pulmonary angioplasty, a catheter‑based procedure that opens narrowed lung arteries.

the procedure is performed after you have been on riociguat and is considered successful when the targeted arteries are reopened.

4 randomization to continuation or discontinuation

following a successful angioplasty, you will be randomly assigned to either keep taking riociguat or stop the medication.

if you are assigned to discontinue, the drug will be withdrawn under medical supervision.

5 regular follow‑up visits

you will return for study visits at month 3, month 6, month 12, and every 6 months thereafter.

each visit includes repeat measurements of the 6‑minute walk distance, reassessment of who functional class, a new nt‑probnp blood test, and the same quality‑of‑life questionnaires.

additional heart pressure measurements may be taken, and you will be asked about any signs of clinical worsening such as hospitalization, worsening heart failure, need for lung transplantation, need for intravenous medications, or a decline of 15 % or more in the walk distance combined with a higher functional class.

6 final study assessment

after at least 12 months of follow‑up, you will complete a final visit that repeats all baseline assessments.

the information collected will be used to compare outcomes between those who continued and those who stopped riociguat.

Who Can Join the Study?

You must sign a written agreement called informed consent that shows you understand the study and agree to either stop or keep taking the medication.
You must be an adult, age 18 years or older.
You must have been diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) that cannot be fixed with surgery, or you still have high blood pressure in the lungs after a surgery called pulmonary endarterectomy (PEA), and you must have reached certain health goals after a procedure called balloon pulmonary angioplasty (BPA). These goals are: your activity level is in World Health Organization functional class I or II (meaning little or no limitation in daily activities); your lung blood‑vessel resistance (pulmonary vascular resistance, PVR) is less than 3 Wood units (a measure of how hard the heart works to push blood through the lungs); and your average pressure in the pulmonary artery (mean pulmonary artery pressure, mPAP) is below 30 mmHg.
You must have taken the medication riociguat alone (no other medicines for this condition) for at least 6 months, and the dose must have been stable (unchanged) for at least the last 3 months.
Your most recent BPA treatment must have been performed at least 6 months before you join the study.
You must be able to walk at least 150 meters in a six‑minute walk test (TM6 ≥ 150 m), which measures your exercise capacity.
If you are a woman who could become pregnant, you must use a highly effective birth‑control method.

Who Cannot Join the Study?

If you are already taking other pulmonary hypertension medicines besides riociguat, such as drugs that block endothelin receptors, phosphodiesterase‑5 inhibitors, prostanoids, or prostacyclin receptor agonists.
If you have serious lung disease that makes breathing difficult, shown by lung tests (FEV₁ less than 60% of normal, FEV₁/FVC less than 65%, or total lung capacity less than 60% of normal) or known conditions like emphysema or interstitial lung disease.
If you have severe liver problems, identified by a Child‑Pugh score of B or C or liver enzyme levels more than three times the normal upper limit.
If you have severe kidney problems, measured by a creatinine clearance of 30 mL/min/1.73 m² or lower.
If you have left‑sided heart failure with a left ventricular ejection fraction (the percentage of blood the heart pumps out) lower than 40%.
If you are currently taking or plan to take organic nitrates, medicines often used for chest pain.
If you are using drugs that strongly increase the activity of the liver enzyme CYP3A4 (examples: rifabutin, rifampicin, carbamazepine, phenobarbital, phenytoin, St. John’s wort).
If you are taking medicines that strongly block transport proteins called P‑glycoprotein (P‑gp) or breast cancer resistance protein (BCRP), such as lopinavir/ritonavir.
If you are in prison or otherwise deprived of liberty by a court decision.
If you are under psychiatric care and cannot give your own consent.
If a court has appointed a guardian or similar legal protector for you.
If you are taking strong CYP3A4 inhibitors (examples: ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, saquinavir) or moderate inhibitors that affect both CYP3A4 and CYP2C9 (examples: fluconazole, amiodarone) or a combination of moderate inhibitors of these enzymes.
If you are unable to give informed consent.
If you are not covered by the national health‑insurance/social security system.
If you have a history of life‑threatening hemoptysis (coughing up more than 100 mL of blood in 24 hours) or have had a bronchial artery embolization procedure to stop such bleeding.
If you are pregnant, breastfeeding, or plan to become pregnant during the study.
If you have other serious illnesses that are expected to shorten your life to less than 12 months, such as active cancer that has spread.
If you have a problem with excessive alcohol use, as judged by the study doctor.
If any condition or situation might make it difficult for you to follow the study rules.
If you are already participating in another interventional clinical trial or are still in the waiting period after finishing one.
If you have post‑capillary pulmonary hypertension, defined by a pulmonary artery wedge pressure (PAWP) greater than 15 mmHg.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Centre Hospitalier Universitaire De Lille	Lille	France
Centre Hospitalier Regional Et Universitaire De Brest	Brest	France
Oncopole Claudius Regaud	Toulouse	France
University Hospital Of Clermont-Ferrand	Clermont Ferrand	France
CHU Grenoble Alpes	La Tronche	France

Other Sites

Site Name	City	Country
Centre Hospitalier Universitaire Rouen	Rouen	France
Centre Hospitalier Universitaire De Nantes	Nantes	France
Hopital Beaujon	Clichy	France
Ihsmnfqs dg Cwxzvtkitnqf Hblbyfouods Uzmnyxibynleo ds Saoxx Eerssfk (qlenpwy	Saint Priest En Jarez	France
Clltgv Hmbucrjbywj Uappuioemdhjl De Ckpd Nifyinnbc	Caen	France
Cjuvwg Hsnhspjedsu Uykzfivwuovof Dc Dhqda	Dijon	France
Aomortytmb Pnrpqnzc Hfjxtgur Dt Meevlqekp	Marseille	France
Ctwhjz Hxwetrktymk Ruyfhcmk Umropmfqhthos Dj Tvhxz	Tours	France
Cpqhng Hejthvbfddl Uxvcghussmtvh Da Mhsdnouvqpo	Montpellier	France
Cgkd Du Noaam	Vandoeuvre Les Nancy	France
Cbwumo Hsugfsohxoz Ukwqstpiltywe Dw Rzuqgk	Rennes	France
Cmywjl Hcdfwhmctyx Urbjaorfwuvlv Dx Pqbziqxl	Poitiers	France
Cuduza Hufgzhaucqo Lapv Sqw	Pierre Benite	France
Cdgdwf Hargquusvne Rvjikxdw Dmqnvxogsbhnut	Angers	France
Hmicrigo Udylltkosojniy Sbvodiayps &bgljbx Hphytik dx Htdqwshmlaa	STRASBOURG, Alsace	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.10.2026

Trial locations

Investigated Drugs:

Riociguat

Riociguat is an oral medication that helps relax and widen the blood vessels in the lungs. By doing this, it lowers the pressure that builds up in the lungs in a condition called chronic thromboembolic pulmonary hypertension (CTEPH). In this study, patients who have already had a successful balloon pulmonary angioplasty are either asked to keep taking riociguat or to stop it, so researchers can see how stopping the drug affects their health over at least a year.

Balloon pulmonary angioplasty (BPA) is a minimally invasive procedure used to treat CTEPH. A thin tube with a tiny balloon at its tip is guided through the blood vessels to the narrowed areas in the lungs. The balloon is then inflated to open the blocked vessels, improving blood flow and reducing pressure in the lungs. In this trial, BPA is performed first, and then the study looks at what happens when patients continue or discontinue riociguat after the procedure.

Chronic thromboembolic pulmonary hypertension – It is a condition where scarred blood clots block the arteries that carry blood from the heart to the lungs, raising pressure in those vessels. The blockage makes the right side of the heart work harder to push blood through the lungs. Over time the heart muscle can become enlarged and less able to pump effectively. As pressure continues to rise, symptoms such as shortness of breath and tiredness may gradually increase. The disease usually progresses slowly, with the blocked areas potentially expanding and further increasing vascular pressure.

Trial ID:

2026-525351-81-00

Protocol code:

APHP251608

Trial Phase:

Therapeutic exploratory (Phase II)

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Discontinuing vs Continuing Riociguat in Chronic Thromboembolic Pulmonary Hypertension Patients After Successful Balloon Pulmonary Angioplasty

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?