Trial Outcomes & Findings for Heterotopic Implantation Of the Edwards-Sapien Transcatheter Aortic Valve in the Inferior VEna Cava for the Treatment of Severe Tricuspid Regurgitation (HOVER) (NCT NCT02339974)

NCT ID: NCT02339974

Last Updated: 2025-06-18

Results Overview

Procedural success will include both device success and no device/procedure related SAE's including: all death, all stroke, MI, new AKI grade 3, life threatening bleeding, major vascular complications (arterial or venous-requiring unplanned intervention), pericardial effusion or tamponade requiring drainage, SVC syndrome. Safety as defined by successful vascular access without unplanned major vascular complication as defined by VARC-2, delivery and retrieval of the transcatheter valve delivery system, correct position of both the vascular stent(s) and transcatheter valve in the IVC, a single valve placed within the IVC, and no need for additional surgery or re-intervention (including drainage of pericardial effusion) with the patient being alive at 30-days.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 15 participants
• Primary outcome timeframe: 30 days
• Results posted on: 2025-06-18

Participant Flow

Participant milestones

Measure	Severe Tricuspid Regurgitation This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Overall Study STARTED	15
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Heterotopic Implantation Of the Edwards-Sapien Transcatheter Aortic Valve in the Inferior VEna Cava for the Treatment of Severe Tricuspid Regurgitation (HOVER)

Baseline characteristics by cohort

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants
Age, Continuous	77.7 years STANDARD_DEVIATION 7.91 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants
Kansas City Cardiomyopathy Questionnaire (KCCQ)	52.4 units on a scale STANDARD_DEVIATION 16.38 • n=5 Participants
6 Minute Walk Test	237.1 Meters STANDARD_DEVIATION 138.14 • n=5 Participants

PRIMARY outcome

Timeframe: 30 days

Procedural success will include both device success and no device/procedure related SAE's including: all death, all stroke, MI, new AKI grade 3, life threatening bleeding, major vascular complications (arterial or venous-requiring unplanned intervention), pericardial effusion or tamponade requiring drainage, SVC syndrome.

Safety as defined by successful vascular access without unplanned major vascular complication as defined by VARC-2, delivery and retrieval of the transcatheter valve delivery system, correct position of both the vascular stent(s) and transcatheter valve in the IVC, a single valve placed within the IVC, and no need for additional surgery or re-intervention (including drainage of pericardial effusion) with the patient being alive at 30-days.

Outcome measures

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Procedural Success	42.86 Percentage of Participants Interval 9.9 to 81.59

PRIMARY outcome

Timeframe: 30 days

Individual patient success is defined by device success and the following: no re-hospitalizations for right sided heart failure or right sided heart failure equivalents including drainage of ascites or pleural effusions, new listing for heart transplant, VAD, or other mechanical support; improvement in one of three variables: KCCQ improvement>15 vs. baseline; 6MWT improvement> 70 meters vs. baseline; or VO2 peak improvement > 6% vs baseline..

Outcome measures

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Individual Patient Success	2 Participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 1 Year

Population: Incomplete data for these follow-up time frames.

Measure of improvement in lower extremity (LE) edema measured by the Villalta Scale. The Villalta Scale is used to assess patients with lower extremity signs and symptoms of swelling, discoloration, or ulceration. The scale evaluates 5 patient reported items (pain, cramps, heaviness, paresthesia, pruritus) and 6 clinician-observed items (pretibial edema, skin induration, hyperpigmentation, pain during calf compression, venous ectasia, redness). Each item is graded on a four-point scale (0=none, 1=mild, 2=moderate, 3=severe). All points are added, resulting in an overall score from 0 to 33. The final Villalta score of 5-9 is mild disease, 10-14 is moderate, and ≥15 is severe disease. A 3.1 point reduction in this scale between time points is associated with improved quality of life.

Outcome measures

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Lower Extremity Edema 30 Days	7.5 Villalta Scale Score Standard Deviation 4.23
Lower Extremity Edema 6 Months	9 Villalta Scale Score Standard Deviation 5.66
Lower Extremity Edema 1 Year	4.7 Villalta Scale Score Standard Deviation 5.51

SECONDARY outcome

Timeframe: 30 days, 6 months, 1 year

Population: Incomplete data for these follow-up time frames.

Occurrence of stroke or transient ischemic attack (TIA) by Valve Academic Research Consortium (VARC-2) criteria. VARC-2 diagnostic criteria defines stroke as a duration of a focal or global neurological deficit ≥ 24 hours; OR <24 hours if available neuroimaging documents a new hemorrhage or infarct; OR the neurological deficit results in death. VARC-2 diagnostic criteria defines TIA as a duration of a focal or global neurological deficit <24 hours, any variable neuroimaging does not demonstrate a new hemorrhage or infarct.

Outcome measures

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Stroke and Transient Ischemic Attack (TIA) 30 Days · Occurence of Stroke or TIA Occurrence	1 Participants
Stroke and Transient Ischemic Attack (TIA) 6 Months · No Occurrence of Stroke or TIA	4 Participants
Stroke and Transient Ischemic Attack (TIA) 6 Months · Occurence of Stroke or TIA Occurrence	0 Participants
Stroke and Transient Ischemic Attack (TIA) 1 Year · No Occurrence of Stroke or TIA	1 Participants
Stroke and Transient Ischemic Attack (TIA) 1 Year · Occurence of Stroke or TIA Occurrence	2 Participants
Stroke and Transient Ischemic Attack (TIA) 30 Days · No Occurrence of Stroke or TIA	6 Participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 1 year

Population: Incomplete data for these follow-up time frames.

Mortality by Valve Academic Research Consortium (VARC-2) criteria. VARC-2 criteria separate All-cause mortality into 'Cardiovascular mortality' and 'Noncardiovascular mortality'. Cardiovascular mortality is defined as any of the following criteria: Death due to proximate cardiac cause (eg, myocardial infarction, cardiac tamponade, worsening heart failure); Death caused by noncoronary vascular conditions such as neurological events, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular disease; All procedure-related deaths, including those related to a complication of the procedure or treatment for a complication of the procedure; All valve-related deaths including structural or nonstructural valve dysfunction or other valve-related adverse events; Sudden or unwitnessed death; Death of unknown cause. Noncardiovascular mortality is defined as any death in which the primary cause of death is clearly related to another condition (eg, trauma, cancer, suicide)

Outcome measures

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Mortality 30 Days · No Occurrence of Death	6 Participants
Mortality 30 Days · Occurrence of Death	1 Participants
Mortality 6 Months · No Occurrence of Death	2 Participants
Mortality 6 Months · Occurrence of Death	2 Participants
Mortality 1 Year · No Occurrence of Death	1 Participants
Mortality 1 Year · Occurrence of Death	2 Participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 1 Year

Population: Incomplete data for these follow-up time frames.

Myocardial Infarction (MI) by Valve Academic Research Consortium (VARC-2) criteria. VARC-2 defines MI as either periprocedural MI (new ischemic symptoms or signs AND elevated cardiac biomarkers within 72 hours after the index procedure), or spontaneous MI (>72hours after the index procedure, any 1 of the following: detection of rise and/or fall of cardiac biomarkers with at least 1 value above the 99th percentile, together with the evidence of myocardial ischemia with either symptoms of ischemia, ECG changes indicative of new ischemia, new pathological Q-waves in at least two contiguous leads, or imaging evidence of a new loss of viable myocardium or new wall motion abnormality; Sudden, unexpected cardiac death involving cardiac arrest, accompanied by new ST elevation or new LBBB, and/or evidence of fresh thrombus by coronary angiogram or at autopsy, or at a time before the appearance of cardiac biomarker in the blood; or Pathological findings of an acute MI).

Outcome measures

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Myocardial Infarction 30 Days · Occurrence of MI	0 Participants
Myocardial Infarction 30 Days · No Occurrence of MI	7 Participants
Myocardial Infarction 6 Months · Occurrence of MI	0 Participants
Myocardial Infarction 1 Year · Occurrence of MI	0 Participants
Myocardial Infarction 6 Months · No Occurrence of MI	4 Participants
Myocardial Infarction 1 Year · No Occurrence of MI	3 Participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 1 Year

Population: Incomplete data for these follow-up time frames.

Occurrence of Acute Kidney Injury (AKI) by Valve Academic Research Consortium (VARC-2) criteria. VARC-2 criteria defines AKI as any of the following: [Stage 1] Increase in serum creatinine to 150-199% OR Urine output <0.5mL/kg/h for >6 but <12hours; [Stage 2] Increase in serum creatinine to 200-299% OR Urine output <0.5 mL/kg/h for >6 but <12hours; or [Stage 3] Increase in serum creatinine to ≥300% OR Urine output <0.3mL/kg/h for ≥24hours OR Anuria for ≥12hours.

Outcome measures

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Acute Kidney Injury 30 Days · No Occurrence of Acute Kidney Injury	5 Participants
Acute Kidney Injury 30 Days · Occurrence of Acute Kidney Injury	2 Participants
Acute Kidney Injury 6 Months · No Occurrence of Acute Kidney Injury	4 Participants
Acute Kidney Injury 6 Months · Occurrence of Acute Kidney Injury	0 Participants
Acute Kidney Injury 1 Year · No Occurrence of Acute Kidney Injury	2 Participants
Acute Kidney Injury 1 Year · Occurrence of Acute Kidney Injury	1 Participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 1 Year

Population: Incomplete data for these follow-up time frames.

Major Vascular Complications by Valve Academic Research Consortium (VARC-2) criteria. VARC-2 defines major vascular complications as: any aortic dissection aortic rupture, annulus rupture, left ventricle perforation, or new apical aneurysm/pseudoaneurysm; Access site or access-related vascular injury leading to death, life threatening or major bleeding, visceral ischemia, or neurological impairment; Distal embolization from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage; The use of unplanned endovascular or surgical intervention associated with death, major bleeding, visceral ischemia or neurological impairment; Any new ipsilateral lower extremity ischemia documented by patient symptoms, physical exam, and/or decreased or absent blood flow on lower extremity angiogram; surgery for access site-related nerve injury; or Permanent access site-related nerve injury.

Outcome measures

Measure	Severe Tricuspid Regurgitation n=7 Participants This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Major Vascular Complications 30 Days · No Occurrence of Major Vascular Complication	6 Participants
Major Vascular Complications 30 Days · Occurrence of Major Vascular Complication	1 Participants
Major Vascular Complications 1 Year · Occurrence of Major Vascular Complication	2 Participants
Major Vascular Complications 6 Months · No Occurrence of Major Vascular Complication	4 Participants
Major Vascular Complications 6 Months · Occurrence of Major Vascular Complication	0 Participants
Major Vascular Complications 1 Year · No Occurrence of Major Vascular Complication	1 Participants

Adverse Events

Severe Tricuspid Regurgitation

Serious events: 7 serious events

Other events: 1 other events

Deaths: 5 deaths

Serious adverse events

Measure	Severe Tricuspid Regurgitation n=7 participants at risk This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Nervous system disorders Stroke and TIA	42.9% 3/7 • Number of events 3 • 1 year
Cardiac disorders Myocardial Infarction	0.00% 0/7 • 1 year
Renal and urinary disorders Acute Kidney Injury	42.9% 3/7 • Number of events 3 • 1 year
Vascular disorders Major vascular complications	42.9% 3/7 • Number of events 3 • 1 year
Cardiac disorders Lower Extremity Edema	85.7% 6/7 • Number of events 6 • 1 year

Other adverse events

Measure	Severe Tricuspid Regurgitation n=7 participants at risk This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava
Gastrointestinal disorders Gastrointestinal Bleed	14.3% 1/7 • Number of events 1 • 1 year
Cardiac disorders Heart Failure	14.3% 1/7 • Number of events 1 • 1 year
Respiratory, thoracic and mediastinal disorders Shortness of Breath	14.3% 1/7 • Number of events 1 • 1 year

Additional Information

Dr. Brian O'Neill

Henry Ford Health

Phone: 313-970-6483

Email: boneil3@hfhs.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place