FDA Approves Clinical Trial of TIVUS System in PAH
The U.S. Food and Drug Administration (FDA) has granted SoniVie permission to begin a pivotal clinical trial of its Therapeutic Intra-Vascular Ultrasound (TIVUS) System in people with pulmonary arterial hypertension (PAH).
This “study will provide important information on the safety and efficacy of the TIVUS System in the treatment of PAH,” Lewis Rubin, MD, emeritus professor of medicine at the University of California, San Diego School of Medicine, said in a press release.
“The initiation of the pivotal study for the TIVUS System, the first controlled study of a device in this indication, is an important advance for the PAH patient and physician communities,” said Alex Rothman, MD, of the University of Sheffield, England.
The TIVUS system is based on a therapeutic catheter (a flexible tube) being developed by SoniVie (formerly known as Cardiosonic). During a right heart catheterization procedure, the catheter is inserted into the pulmonary artery. Then, using high-energy sound waves (ultrasound), the catheter selectively destroys the nerves that cause the pulmonary artery to constrict, ultimately reducing the blood pressure in the artery and easing PAH symptoms.
“The TIVUS System has the potential to address PAH at a physiologic level by selectively ablating [destroying] nerves associated with disease activity, specifically targeting the cause of disease without the systemic exposure and attendant side effects associated with pharmacotherapy [treatment using medications],” Rubin said.
TIVUS was recognized as a breakthrough device by the FDA in 2019. That designation is meant to speed the development and approval of medical equipment with the potential to provide a greater benefit to patients than available treatments.
A previous feasibility clinical trial, called TROPHY1 (NCT02835950 and NCT02516722), evaluated the TIVUS system in 23 people with PAH. Results from the trial supported its safety and effectiveness, as no serious procedure-related side effects were reported up to one year after the procedure, and there were significant decreases in PAH markers including pulmonary artery pressure.
After a year of treatment, most of the participants available for assessment had a combined hemodynamics (the dynamics of blood flow), functional capacity, and clinical risk score that was either improved (58%) or maintained (32%).
“The 12-month TROPHY1 data are extremely promising and support the potential of the TIVUS System to transform the care and outcomes for patients with PAH,” said Rothman. Both Rothman and Rubin were investigators in the TROPHY1 trial.
“Improvements in pulmonary artery pressure while maintaining baseline metrics in multiple indicators of hemodynamic function and functional capacity are especially encouraging given that patients with PAH typically see declines in these endpoints over time,” Rothman said. “Based on the TROPHY1 data, I am optimistic that the results of the pivotal study will provide additional validation of this innovative technology.”
The upcoming clinical trial (NCT04570228) will be conducted at 25 sites in the U.S., Europe, Israel and Australia. In order to be eligible, participants must have documented PAH, functional class II or III, and be taking at least two medications.
Participants will be assigned randomly to treatment with the TIVUS system or to a sham procedure; in the sham group, the catheter still will be inserted into the pulmonary artery, but no nerve-killing ultrasound will be applied.
The study’s main measurement of effectiveness is the difference in six minute walk test (6MWT) results between the groups after six months. The 6MWT measures the distance a person can walk in six minutes; it is commonly used to measure physical function in ambulatory people.
After six months, participants initially given the sham procedure will be allowed to undergo the active treatment.
The trial is not yet recruiting participants.