Clinical trial NCT01369407: REGISTRY EVALUATION OF VITAL INFORMATION FOR VADs IN AMBULATORY LIFE
Official title: REVIVE-IT Registry (REVIVAL: Registry Evaluation of Vital Information For VADs in Ambulatory Life)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congestive Heart Failure
Keywords: Heart failure
HF
Heart Diseases
Cardiovascular Diseases
Heart Failure NYHA class III
Advanced heart failure
Systolic Heart Failure
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Brigham and Women's Hospital
First posted: 2011-06-08
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Medical records should be reviewed to assess for potential enrollment into the REVIVE-IT Registry. Heart failure subjects that meet all criteria should be approached to consent for this study.

Brief summary: REVIVAL will establish a prospective, observational, multicenter patient cohort in ambulatory patients with chronic, advanced, systolic heart failure that will provide a greater understanding of their clinical trajectory (rates of hospitalizations, transplantation, MCSD use and death), and of how baseline clinical risk measures are related to prognosis.

Detailed description: REVIVAL will establish a prospective, observational, multicenter patient cohort in ambulatory patients with chronic, advanced, systolic heart failure that will provide a greater understanding of their clinical trajectory (rates of hospitalizations, transplantation, MCSD use and death), and of how baseline clinical risk measures are related to prognosis. Within the broader goal of 1) improving prognostic assessment in chronic, ambulatory, advanced systolic heart failure, additional targeted goals are to 2) better inform the selection of appropriate candidates for a future study of a strategy of early LVAD therapy vs. optimal medical management in this population, and 3) determine the feasibility of identifying candidates for such a trial. Therefore, the target population will have known high-risk features for increased mortality and hospitalization (e.g., frequent hospitalization, reduced exercise capacity, elevated BNP or N-terminal proBNP, increased Seattle Heart Failure Model risk score, reduced Heart Failure Survival Score).

The REVIVE-IT Registry (i.e., REVIVAL) is a prospective cohort study to be conducted in up to twenty five (25) participating Clinical Sites in the USA. The study will continue until up to 400 eligible heart failure heart failure subjects have been enrolled (estimated length of accrual is 12 months).

Eligibility criteria: Inclusion Criteria:

1. Ambulatory.
2. Chronic systolic heart failure ≥ 12 months.
3. NYHA II - IV for at least 45 of the last 60 days.
4. Last documented left ventricular ejection fraction ≤ 35% by any imaging modality.
5. Age 18 - 80 years.
6. Under the care of a cardiologist at study site.
7. On appropriate evidenced -based heart failure medications - ACE inhibitor, ARB or sacubitril/valsartan \[LCZ-696\]; beta blocker; aldosterone antagonist; hydralazine/long-acting nitrate \[required of African-American subjects only\] for ≥ 3 months absent contraindications or intolerances.
8. Has ICD or CRT-D. If CRT-D, present for ≥ 3 months.
9. Demonstrated advanced heart failure, including any one of the following\*:

   i. Serum sodium ≤ 135 mEq/L (obtained as an outpatient)\*\* ii. Serum BNP ≥ 750 pg/mL or NT-proBNP ≥ 3000 pg/mL\*\* (obtained as an outpatient) iii. Seattle Heart Failure Model (SHFM) one year predicted survival ≤ 85%\*\* iv. Heart Failure Survival Score (HFSS) ≤ 7.19\*\* v. Peak VO2 ≤ 55% of predicted for age by Wasserman equation or ≤ 14 ml/kg/min, with RER ≥ 1.05\*\*\* vi. VE/VC02 slope \> 40\*\*\* vii. 6 minute walk test (6MWT) distance ≤ 350 m without significant non-cardiac limitation\*\* viii. Currently listed as Heart Transplant Status II due to heart failure limitation

   Or

   History of one (1) hospitalization (≥ 24 hours) for acute or acute on chronic heart failure in the past year with additional history to include:

   i. Serum BNP ≥ 500 pg/mL or NT-proBNP ≥ 2000 pg/mL\*\* (obtained as an outpatient)

   Or

   History of two (2) hospitalizations (≥ 24 hours) for acute or acute on chronic heart failure in the past year.

   \* Qualifying measure must be the most recent of that type of measure obtained (i.e., a BNP ≥ 1000 obtained 2 months prior would not qualify the heart failure subject if a more recent BNP was \< 1000)

   \*\*Using values obtained within the prior 90 days, except for peak VO2 within 365 days

   \*\*\*Obtained within the prior 365 days
10. Willingness to continue to receive heart failure care from the enrolling advanced heart failure clinic over the next two (2) years and to come for all scheduled study visits.

12. Written Informed consent given.

Exclusion Criteria:

1. Known serious medical problem other than heart failure that would be expected to limit 2-year survival (≥50% mortality within 2 years from non-heart failure diagnosis).
2. Patient is not likely to be compliant with the protocol, in the opinion of the Investigator.
3. Currently hospitalized.
4. Current use of an intravenous inotrope.
5. Primary functional limitation from non-cardiac diagnosis even if not likely to limit survival.
6. Chronic hemodialysis or peritoneal dialysis or a serum creatinine value of ≥ 3 mg/dL at time of enrollment.
7. Cardiac amyloidosis, cardiac sarcoidosis, constrictive pericardial disease, active myocarditis or congenital heart disease with significant structural abnormality.
8. Hypertrophic cardiomyopathy unless dilated LV and no outflow gradient.
9. Cardiac conditions that are amenable to surgical or percutaneous procedures (other than VAD or transplant) that would substantially improve prognosis and for which this subject is a reasonable candidate, regardless of whether the procedure will or will not be performed.
10. Uncorrected hyperthyroidism or hypothyroidism.
11. Pregnancy.

Primary outcomes:
measure: To characterize clinical outcomes, quality of life and functional impairment over two (2) years in a population of ambulatory patients on evidence-based therapy with advanced chronic systolic heart failure who may benefit from VAD therapy
timeFrame: 2 years
measure: To evaluate the relationship between heart failure subject's modeled prognosis, self assessed prognosis, preferences for end of life care and thresholds for considering VAD implant.
timeFrame: 2 years
measure: To evaluate caregiver burden associated with heart failure subject's measures of heart failure severity, quality of life, functional limitations and with preferences for care and thresholds for considering device implant.
timeFrame: 2 years.
measure: To determine health-associated costs for heart failure subjects in the registry.
timeFrame: 2 years.
measure: To provide the REVIVE-IT Registry to the INTERMACS study group to be used in comparative analyses of outcomes of patients treated with medical versus VAD therapy.
timeFrame: 2 years.
Secondary outcomes:
measure: Hospitalization
timeFrame: 2 years
measure: Stroke
timeFrame: 2 years
measure: MCSD
timeFrame: 2 years
measure: Transplant
timeFrame: 2 years
measure: Death
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Care Foundation
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS
state: Oklahoma
city: Abington
country: United States
facility: Abington Jefferson Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: University of Michigan
name: Keith Aaronson, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Garrick Stewart, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington - St. Louis
name: Doug Mann, MD
role: STUDY_CHAIR
References:
citation: Cascino TM, Colvin MM, Lanfear DE, Richards B, Khalatbari S, Mann DL, Taddei-Peters WC, Jeffries N, Watkins DC, Stewart GC, Aaronson KD; REVIVAL Investigators. Racial Inequities in Access to Ventricular Assist Device and Transplant Persist After Consideration for Preferences for Care: A Report From the REVIVAL Study. Circ Heart Fail. 2023 Jan;16(1):e009745. doi: 10.1161/CIRCHEARTFAILURE.122.009745. Epub 2022 Oct 19.
citation: Lala A, Shah KB, Lanfear DE, Thibodeau JT, Palardy M, Ambardekar AV, McNamara DM, Taddei-Peters WC, Baldwin JT, Jeffries N, Khalatbari S, Spino C, Richards B, Mann DL, Stewart GC, Aaronson KD, Mancini DM; REVIVAL Investigators. Predictive Value of Cardiopulmonary Exercise Testing Parameters in Ambulatory Advanced Heart Failure. JACC Heart Fail. 2021 Mar;9(3):226-236. doi: 10.1016/j.jchf.2020.11.008. Epub 2021 Feb 3.
citation: Cascino TM, Kittleson MM, Lala A, Stehlik J, Palardy M, Pamboukian SV, Ewald GA, Mountis MM, Horstmanshof DA, Robinson SW, Shah P, Jorde UP, McLean RC, Richards B, Khalatbari S, Spino C, Taddei-Peters WC, Grady KL, Mann DL, Stevenson LW, Stewart GC, Aaronson KD; REVIVAL Investigators. Comorbid Conditions and Health-Related Quality of Life in Ambulatory Heart Failure Patients: REVIVAL (Registry Evaluation of Vital Information for VADs in Ambulatory Life REVIVAL). Circ Heart Fail. 2020 May;13(5):e006858. doi: 10.1161/CIRCHEARTFAILURE.119.006858. Epub 2020 May 18.
citation: Pagani FD, Aaronson KD, Kormos R, Mann DL, Spino C, Jeffries N, Taddei-Peters WC, Mancini DM, McNamara DM, Grady KL, Gorcsan J 3rd, Petrucci R, Anderson AS, Glick HA, Acker MA, Eduardo Rame J, Goldstein DJ, Pamboukian SV, Miller MA, Timothy Baldwin J; REVIVE-IT Investigators. The NHLBI REVIVE-IT study: Understanding its discontinuation in the context of current left ventricular assist device therapy. J Heart Lung Transplant. 2016 Nov;35(11):1277-1283. doi: 10.1016/j.healun.2016.09.002. Epub 2016 Oct 6.