What side effects are associated with this type of intervention?

Common treatments for exercise intolerance, such as soluble guanylate cyclase stimulators like Riociguat, often have side effects including headache, dizziness, dyspepsia, peripheral edema, and hypotension. Endothelin receptor antagonists like bosentan, another treatment option, typically present mild side effects that are similar in frequency to those seen with placebo.

What prior FDA approvals exist?

Riociguat, a soluble guanylate cyclase stimulator, is FDA-approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), both of which can cause exercise intolerance. Other FDA-approved treatments for PAH that may improve exercise capacity include endothelin receptor antagonists (e.g., bosentan, ambrisentan, macitentan) and phosphodiesterase type 5 inhibitors (e.g., sildenafil, tadalafil). These medications work through different mechanisms to reduce pulmonary vascular resistance and improve exercise tolerance.

What other types of research exist?

Promising novel alternatives to Riociguat for treating exercise intolerance in 2024 include Selexipag (an oral prostacyclin receptor agonist) and Sotatercept (an activin receptor type IIA fusion protein). Both have shown potential in recent clinical trials for improving exercise capacity in patients with pulmonary hypertension.

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Soluble Guanylate Cyclase Stimulators

Adempas for Exercise Intolerance in Pulmonary Hypertension

Phase 2

Recruiting

Led By Todd Bull, MD

Research Sponsored by University of Colorado, Denver

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adult patients who underwent PTE for Chronic thromboembolic pulmonary hypertension (CTEPH) at least six months prior to screening and report ongoing subjective exercise limitation

Be older than 18 years old

Must not have

Patients with known Residual Pulmonary Hypertension (RPH) by RHC following PTE for CTEPH

Ongoing PAH-specific vasodilator therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and 3 months

Awards & highlights

No Placebo-Only Group

All Individual Drugs Already Approved

Approved for 5 Other Conditions

Summary

This trial studies Riociguat, a medication that helps widen blood vessels, in patients who still have trouble exercising several months after pulmonary endarterectomy surgery. The goal is to improve their ability to exercise by enhancing blood flow.

Who is the study for?

This trial is for adults who had surgery (PTE) for a type of high blood pressure in the lungs caused by clots (CTEPH) at least six months ago and still feel limited when exercising. They must be able to consent and perform exercise tests but can't join if they have ongoing lung pressure issues, are on certain lung medications, or can't take Riociguat due to other health risks.

What is being tested?

The study is testing Adempas (Riociguat), a medication, on patients who still experience difficulty with physical activity after having surgery for pulmonary hypertension due to blood clots. It's an open-label trial, meaning everyone knows they're getting the drug, not a placebo.

What are the potential side effects?

Adempas may cause side effects like dizziness, headaches, low blood pressure when standing up, stomach problems like nausea or vomiting, bleeding issues such as nosebleeds or coughing up blood.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I had surgery for CTEPH over 6 months ago and still feel limited in my ability to exercise.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have high blood pressure in my lungs after surgery for CTEPH.

Select...

I am currently on medication to widen my blood vessels for PAH.

Select...

I have a physical limitation that prevents me from completing exercise routines.

Select...

I cannot take riociguat due to health reasons.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and 3 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and 3 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and 3 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Pulmonary artery compliance

Change in cardiac output

Change in mean pulmonary arterial pressure

Secondary study objectives

Change in 6 minute walk test

Change in New York Heart Association (NYHA) functional class

Change in the University of California San Diego (UCSD) shortness of Breath Score

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Study DrugExperimental Treatment1 Intervention

Riociguat (Adempas) 0.5mg to 2.5 mg three time daily - oral medication

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Riociguat, a soluble guanylate cyclase (sGC) stimulator, works by enhancing the nitric oxide (NO) signaling pathway, leading to vasodilation and improved blood flow. This mechanism is crucial for patients with exercise intolerance as it helps reduce pulmonary vascular resistance and improve oxygen delivery to tissues during physical activity. Other common treatments, such as phosphodiesterase-5 inhibitors (e.g., sildenafil), also enhance NO signaling by preventing the breakdown of cyclic GMP, further promoting vasodilation. Endothelin receptor antagonists (e.g., bosentan) block the effects of endothelin-1, a potent vasoconstrictor, thereby reducing vascular resistance. These treatments are vital for improving exercise capacity and reducing symptoms in patients with exercise intolerance by optimizing pulmonary and systemic circulation.

Pharmacological and nonpharmacological interventions to improve symptom control, functional exercise capacity and quality of life in interstitial lung disease: an evidence synthesis.