Protocol feasibility for catheter-based cardiovascular devices: designing first-in-human endpoints for same-day observation

Many first-in-human protocols for catheter-based cardiovascular devices are written as if every participant will spend the night in a hospital. Sometimes that is right. Often it is a default copied from a pivotal study template, and it quietly decides which sites can run the study, what each patient costs and how fast enrollment moves.

I'm Julio Martinez-Clark, CEO of Amavita Research. We run cardiovascular trials in Miami, including early-phase device work at our affiliated cardiovascular ambulatory surgery center in Kendall. This article is for chief medical officers and founders designing early feasibility protocols for endovascular, structural heart and vascular intervention devices, and it covers how to design endpoints that allow same-day observation when the science supports it.

The short answer

If the procedure risk profile allows discharge on the same day, design the protocol around a defined post-procedure observation window with continuous telemetry, scheduled labs and a pre-discharge assessment, then follow up by phone and clinic visit. That design widens the pool of qualified sites and lowers facility overhead. If the device carries a real risk of delayed events that need inpatient management, keep admission in the protocol and choose a hospital site.

Inpatient vs outpatient feasibility: what the endpoint design decides

Three protocol choices shape almost everything downstream:

• Observation period. A fixed overnight stay requires a hospital bed. A defined observation window of several hours with clear discharge criteria can fit an ambulatory setting.
• Primary safety endpoint timing. Endpoints assessed at discharge, 30 days and later can be captured in an outpatient model. Endpoints that require repeated inpatient measurements cannot.
• Discharge criteria. Clear, protocol-defined criteria such as hemostasis, ambulation, stable rhythm, stable labs and a normal access-site check let investigators make consistent decisions.

Each of these also drives per-patient facility overhead and how many sites can realistically run the study. A protocol that needs an inpatient bed for every participant narrows you to hospitals with research bed capacity, which are also the sites with the longest startup queues. It also shapes the participant experience. A patient who can go home the same day, with a clear follow-up plan, is often more willing to enroll and to come back for later visits, and that matters for retention in a small early cohort where every follow-up data point counts.

Essential monitoring parameters for same-day designs

A same-day protocol is not a lighter protocol. It moves the safety work into a shorter, more structured window. The elements we scope with sponsors:

• Continuous ECG telemetry through the observation window, with defined alarm thresholds and response steps.
• Hemodynamic monitoring during the procedure and serial vital signs afterward.
• Serial blood draws at protocol-defined times, for example cardiac biomarkers, hemoglobin and renal function after contrast, with processing and shipping planned in advance.
• Access-site assessment at fixed intervals, plus pre-discharge imaging such as duplex ultrasound when the device or access route calls for it.
• A pre-discharge investigator review documented against the protocol criteria.
• Early contact, such as a next-day phone call, followed by scheduled clinic visits.

At Amavita Research, this runs inside the affiliated ASC, which has a cath lab and procedure suites and 8 monitored observation beds with continuous ECG telemetry. Stays are same-day and built to fit ASC admit-and-discharge rules, and monitoring, sampling and dosing windows are confirmed with each sponsor during feasibility.

Safety reporting does not change with the setting

Outpatient design does not relax any regulatory duty. For significant-risk devices as defined in 21 CFR 812.3(m), the IDE rules apply in full. Investigators must report an unanticipated adverse device effect to the sponsor and the reviewing IRB within 10 working days of learning of it under 21 CFR 812.150(a)(1). ISO 14155:2020 provides the adverse event and device deficiency classifications most sponsors use across US and non-US sites.

What does change is the plan for events after discharge. A same-day protocol needs a written process for how participants reach the site after hours, how the site captures events treated elsewhere and how those events reach the sponsor on time.

Use the endpoint definitions your field already accepts

Early feasibility data is more useful when it speaks the same language as the pivotal study it will inform. For coronary devices, many sponsors align with the Academic Research Consortium definitions (ARC-2). For transcatheter valve work, the Valve Academic Research Consortium definitions (VARC-3) are the common reference. Using standard definitions from the start makes it easier to pool early cases with later data and to present them to FDA.

FDA's 2013 guidance on IDEs for early feasibility studies supports starting human work earlier in device development, with the expectation that the device may change. Design the protocol so that device iterations, and the reasons for them, are documented in a way that survives later review.

Multimodal protocols: imaging without losing coordination

Many catheter-based device protocols need imaging beyond the procedure itself: CT angiography for anatomy screening, echocardiography for structural endpoints, MRI for selected tissue or flow questions. Not every site hosts every modality. The questions that matter:

• Where will each imaging study be performed, and under which agreements?
• Who reads the images, and is a core lab involved?
• How are imaging dates kept inside protocol windows?
• Does all of it stay inside one site regulatory file and one delegation log?

We scope imaging sources during feasibility for each protocol. We describe how imaging fits into protocol execution in imaging-enabled expansion and protocol execution in cardiovascular trials.

Investigator selection: procedure volume and attention

The best early feasibility investigators combine two things: they perform the procedure class routinely, and they have time to think about the protocol. In busy hospital departments, research cases compete with emergency and scheduled clinical work, and the investigator who championed the study may not be the one in the room.

Our team includes interventional, structural-heart and electrophysiology investigators who practice inside Amavita Heart and Vascular Health®, so pre-screening starts from patients they already see. For sponsors, that means the physician who reviews eligibility is usually the physician who performs the procedure and follows the participant.

A protocol feasibility checklist

• Does the procedure risk profile support same-day discharge, and what evidence supports that?
• Is the observation window defined in hours, with objective discharge criteria?
• Which labs, at what times, and where will samples be processed?
• What pre-discharge imaging is required, and can the site perform it?
• Which standard endpoint definitions will the protocol use?
• How will post-discharge events be captured and reported within regulatory timelines?
• What imaging is needed outside the procedure, and who will read it?
• How many eligible patients does the site see each month for this indication?

When to keep admission in the protocol

Same-day design is a tool, not a goal. Keep inpatient observation when early experience with the device class shows delayed complications that need hospital management, when the procedure requires general anesthesia with extended recovery, or when FDA has asked for it. In those cases a hospital site is the right choice, and a hybrid design can still use an ASC site for follow-up or for later, lower-risk cohorts.

Review trial feasibility and investigator credentials for your cardiovascular protocol at amavitaresearch.com. Send the protocol synopsis and the observation plan, and we will tell you whether a same-day design fits and what it would take to run it.