NODE-1: Simple Nasal Spray May Short-circuit Acute PSVT

Patrice Wendling

May 16, 2017

CHICAGO, IL — A nasal spray containing the calcium-channel blocker etripamil could allow patients to convert acute paroxysmal supraventricular tachycardia (PSVT) outside the hospital, phase 2 data from the Intranasal Etripamil for the Conversion of PSVT to Sinus Rhythm (NODE-1) trial suggest[1].

Patients with PSVT awaiting ablation treated with 35-, 70-, 105-, and 140-mg intranasal etripamil returned to normal sinus rhythm in a median of 2 to 3 minutes, with 65%, 87%, 75%, and 95%, respectively, converting within 15 minutes compared with 35% given placebo (P<0.05 for the 70-, 105-, and 140-mg doses).

Transient reductions in blood pressure were seen at the two higher doses, but overall etripamil had an acceptable safety profile and was well tolerated.

"If successful, etripamil could provide a fast-acting nasal spray that can safely terminate acute PSVT without the need for an urgent-care visit and could change the treatment paradigm for acute management of PSVT," study author Dr Bruce Stambler (Piedmont Heart Institute, Atlanta, GA) said in a late-breaking clinical-trial session at the Heart Rhythm Society (HRS) Scientific Sessions 2017.

If vagal maneuvers don't terminate acute PSVT, intravenous use of beta-blockers, diltiazem, or the calcium-channel blocker verapamil is highly effective but inconvenient and increases healthcare utilization, he said in a press briefing on the study.

Briefing cochair Dr Jeanne Poole (University of Washington Medical Center, Seattle) said, "It's been a long time since we've seen any new medication come on board that might be useful for these patients. So I'm excited about these results. I think it could be a game-changer, but again these are the first results."

If confirmed, though, "this could be practically very useful for patients to be able to treat themselves at home," she said.

NODE-1 was conducted at 35 centers in the US and Canada and prospectively treated 104 patients (mean age 52.2 years; 57% female) with etripamil or placebo. Atrioventricular nodal reentrant tachycardia was the most common mechanism of tachycardia. The mean SVT rate was 162 bpm.

The 70-mg dose appeared to be the "sweet spot" and will be carried forward to a phase 3 trial being planned, Stambler said.

Dr Thomas Deering (Piedmont Heart Institute, Atlanta, GA) said patient selection will be critical going forward.

"We've got to be very careful if it ever reaches FDA approval that it is appropriately defined for the right person and the right reason because otherwise nefarious effects can occur," he said at the briefing. "So I think we have to wait for those studies, but potentially it has an impact that could be significant."

Stambler said NODE-1 excluded patients with ventricular preexcitation (Wolff-Parkinson-White syndrome) and that it would be important to rule out these patients before etripamil could be used in the community, noting reports of rhythm disturbances with verapamil.

"It will be important in my judgment to exclude those patients and make sure that patients have documented narrow complex tachycardia first, no preexcitation. I think patients in the phase 3 trial will likely need some kind of event monitor, so that we can further understand the compound outside the hospital environment," he added.

Patients treated with etripamil in NODE-1 reported nasal discomfort and congestion and throat irritation, but this was minimized after being instructed to keep their chin down during drug administration. There were nine cough events, one of which was severe in a patient given etripamil 105 mg.

Briefing cochair Dr Andrew Krahn (University of British Columbia, Vancouver) said, "The Achilles' heel of this whole thing is going to be the safety of it and whether it's safe for a person to do this at home."

That said, etripamil has the potential to disrupt current thinking of PSVT as a problem readily fixed with ablation.

"Here's the disruptive way of thinking of this: Imagine SVT is like a migraine. You get a migraine, you take your shot, right? So instead of it being something that's a fixable problem, it's a manageable problem with a home remedy," Krahn said.

He also noted that "there may be an element of this population, particularly if they get SVT in a later stage in life, who would rather use a medical approach to this once or twice a year rather than undergo an invasive procedure, even if from our perspective it's a procedure that seems simple and acceptable."

Poole countered that the two approaches aren't mutually exclusive and that "etripamil could be something offered to patients while waiting for a definitive procedure."

The trial was funded by Milestone Pharmaceuticals and conducted by Medpace. Stambler reports compensation for consulting services for Boston Scientific and Medtronic and serving as an unpaid advisor to Milestone. Coauthor disclosures are listed in the abstract. Poole reports compensation for services from Zoll Medical, Physio Control, St Jude Medical, Biotronik, Medtronic, and Boston Scientific; fellowship support from Biotronik, Boston Scientific, Medtronic, and St Jude Medical; and other relationships with Mediasphere Medical and the American College of Cardiology. Deering disclosed serving as a speaker for Boston Scientific; recently divesting an equity interest in CorMatrix and Zywie; research funding to his institution from CorMatrix, Spectranetics, Sorin Group, Boston Scientific, Medtronic, and St Jude Medical; and other compensation from Medtronic and Boston Scientific. Krahn reports no relevant financial relationships.

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