Current or Recent History of Atrial Fibrillation Clinical Trial
— GENETIC-AFOfficial title:
GENETIC-AF - A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure
| Verified date | September 2022 |
| Source | ARCA Biopharma, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study is being done to compare the effects of bucindolol hydrochloride (bucindolol) to metoprolol succinate (Toprol-XL) on the recurrence of symptomatic atrial fibrillation/atrial flutter in patients with heart failure who have a specific genotype for the beta-1 adrenergic receptor.
| Status | Completed |
| Enrollment | 267 |
| Est. completion date | December 28, 2017 |
| Est. primary completion date | December 28, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 85 Years |
| Eligibility | Key Inclusion Criteria: - Must weigh at least 40 kg - Possess the ß1389 Arg/Arg genotype - Left Ventricular Ejection Fraction (LVEF) < 0.50 assessed within 12 months prior to Screening - At least one episode of symptomatic paroxysmal or persistent AF within 180 days of Screening - Clinically appropriate for electrical cardioversion (ECV) if AF/AFL is present after study drug initiation - Receiving appropriate anticoagulation therapy prior to Randomization Key Exclusion Criteria: - NYHA Class IV symptoms at the time of Randomization - Significant fluid overload at Randomization - Permanent AF at Screening - More than two previous ECV within 6 months of Randomization or if the most recent ECV failed to produce SR - Presence of an LVAD, or likely to requirement LVAD placement within 6 months of Randomization - History of a successful atrioventricular (AV) node ablation - History of an AF/AFL ablation within 30 days of Randomization - Evidence of an appropriate firing of an implanted cardioverter-defibrillator (ICD) device for ventricular tachycardia (VT) or ventricular fibrillation (VF) within 90 days of Randomization |
| Country | Name | City | State |
|---|---|---|---|
| Canada | ARCA Clinical Research Site #612 | Calgary | Alberta |
| Canada | ARCA Clinical Research Site #611 | Cambridge | Ontario |
| Canada | ARCA Clinical Research Site #621 | Cambridge | Ontario |
| Canada | ARCA Clinical Research Site #601 | Hamilton | Ontario |
| Canada | ARCA Clinical Research Site #609 | London | Ontario |
| Canada | ARCA Clinical Research Site #603 | Montreal | Quebec |
| Canada | ARCA Clinical Research Site #607 | Montreal | Quebec |
| Canada | ARCA Clinical Research Site #614 | Montreal | Quebec |
| Canada | ARCA Clinical Research Site #623 | Newmarket | Ontario |
| Canada | ARCA Clinical Research Site #618 | Oshawa | Ontario |
| Canada | ARCA Clinical Research Site #613 | Ottawa | Ontario |
| Canada | ARCA Clinical Research Site #615 | Quebec | |
| Canada | ARCA Clinical Research Site #625 | Saint-Jerome | Quebec |
| Canada | ARCA Clinical Research Site #602 | Sherbrooke | Quebec |
| Canada | ARCA Clinical Research Site #619 | Toronto | Ontario |
| Canada | ARCA Clinical Research Site #626 | Trois-Rivières | Quebec |
| Canada | ARCA Clinical Research Site #624 | Vancouver | British Columbia |
| Canada | ARCA Clinical Research Site #616 | Waterloo | Ontario |
| Hungary | ARCA Clinical Research Site #726 | Budapest | |
| Hungary | ARCA Clinical Research Site #727 | Budapest | |
| Hungary | ARCA Clinical Research Site #728 | Budapest | |
| Hungary | ARCA Clinical Research Site #729 | Budapest | |
| Hungary | ARCA Clinical Research Site #733 | Debrecen | |
| Hungary | ARCA Clinical Research Site #732 | Kaposvar | |
| Hungary | ARCA Clinical Research Site #730 | Pecs | |
| Hungary | ARCA Clinical Research Site #731 | Szeged | |
| Hungary | ARCA Clinical Research Site #734 | Szolnok | |
| Netherlands | ARCA Clinical Research Site #781 | Capelle aan den IJssel | |
| Netherlands | ARCA Clinical Research Site #779 | Gorinchem | |
| Netherlands | ARCA Clinical Research Site #776 | Groningen | |
| Netherlands | ARCA Clinical Research Site #780 | Helmond | |
| Netherlands | ARCA Clinical Research Site #782 | Leiderdorp | |
| Netherlands | ARCA Clinical Research Site #786 | Roosendaal | |
| Netherlands | ARCA Clinical Research Site #777 | Sneek | |
| Netherlands | ARCA Clinical Research Site #783 | Stadskanaal | |
| Netherlands | ARCA Clinical Research Site #784 | Tiel | |
| Poland | ARCA Clinical Research Site #752 | Bialystok | |
| Poland | ARCA Clinical Research Site #757 | Gdansk | |
| Poland | ARCA Clinical Research Site #753 | Krakow | |
| Poland | ARCA Clinical Research Site #751 | Lodz | |
| Poland | ARCA Clinical Research Site #755 | Lodz | |
| Poland | ARCA Clinical Research Site #758 | Lublin | |
| Poland | ARCA Clinical Research Site #754 | Warsaw | |
| Poland | ARCA Clinical Research Site #756 | Wroclaw | |
| Serbia | ARCA Clinical Research Site #806 | Belgrade | |
| Serbia | ARCA Clinical Research Site #807 | Belgrade | |
| Serbia | ARCA Clinical Research Site #801 | Kragujevac | |
| Serbia | ARCA Clinical Research Site #804 | Niš | |
| Serbia | ARCA Clinical Research Site #805 | Niš | |
| United States | ARCA Clinical Research Site #173 | Akron | Ohio |
| United States | ARCA Clinical Research Site # 179 | Albany | New York |
| United States | ARCA Clinical Research Site #157 | Anchorage | Alaska |
| United States | ARCA Clinical Research Site #351 | Athens | Georgia |
| United States | ARCA Clinical Research Site #389 | Atlanta | Georgia |
| United States | ARCA Clinical Research Site #153 | Aurora | Colorado |
| United States | ARCA Clinical Research Site #398 | Baltimore | Maryland |
| United States | ARCA Clinical Site #391 | Charlottesville | Virginia |
| United States | ARCA Clinical Research Site #392 | Cincinnati | Ohio |
| United States | ARCA Clinical Research Site #322 | Cleveland | Ohio |
| United States | ARCA Clinical Research Site #151 | Columbus | Ohio |
| United States | ARCA Clinical Research Site #387 | Dallas | Texas |
| United States | ARCA Clinical Research Site #380 | Denver | Colorado |
| United States | ARCA Clinical Research Site #181 | Durham | North Carolina |
| United States | ARCA Clinical Research Site #381 | East Palo Alto | California |
| United States | ARCA Clinical Research Site #161 | Elmer | New Jersey |
| United States | ARCA Clinical Research Site #386 | Falls Church | Virginia |
| United States | ARCA Clinical Site #393 | Germantown | Tennessee |
| United States | ARCA Clinical Research Site #349 | Greensboro | North Carolina |
| United States | ARCA Clinical Research Site #303 | Hammond | Indiana |
| United States | ARCA Clinical Research Site # 189 | Hershey | Pennsylvania |
| United States | ARCA Clinical Research Site #202 | Hillsborough | New Jersey |
| United States | ARCA Clinical Research Site #388 | Iowa City | Iowa |
| United States | ARCA Clinical Research Site #198 | Jackson | Tennessee |
| United States | ARCA Clinical Research Site #109 | Lancaster | Pennsylvania |
| United States | ARCA Clinical Research Site #152 | Lincoln | Nebraska |
| United States | ARCA Clinical Research Site #186 | Loma Linda | California |
| United States | ARCA Clinical Research Site #200 | Manassas | Virginia |
| United States | ARCA Clinical Research Site #195 | Miami | Florida |
| United States | ARCA Clinical Research Site #156 | Minneapolis | Minnesota |
| United States | ARCA Clinical Site #396 | New Orleans | Louisiana |
| United States | ARCA Clinical Research Site #397 | New York | New York |
| United States | ARCA Research Site #131 | Norfolk | Virginia |
| United States | ARCA Clinical Research Site #342 | Oakbrook Terrace | Illinois |
| United States | ARCA Clinical Research Site #399 | Oklahoma City | Oklahoma |
| United States | ARCA Clinical Research Site #320 | Pasadena | California |
| United States | ARCA Clinical Research Site #133 | Philadelphia | Pennsylvania |
| United States | ARCA Clinical Research Site #383 | Phoenix | Arizona |
| United States | ARCA Clinical Research Site #385 | Phoenix | Arizona |
| United States | ARCA Clinical Research Site #115 | Portland | Oregon |
| United States | ARCA Clinical Research Site #196 | Puyallup | Washington |
| United States | ARCA Clinical Research Site #108 | Saint Louis | Missouri |
| United States | ARCA Clinical Research Site #201 | Saint Louis | Missouri |
| United States | ARCA Clinical Research Site #174 | Saint Paul | Minnesota |
| United States | ARCA Clinical Research Site #379 | Salt Lake City | Utah |
| United States | ARCA Clinical Research Site #390 | Stanford | California |
| United States | ARCA Clinical Research Site #184 | Tampa | Florida |
| United States | ARCA Clinical Research Site #127 | Ypsilanti | Michigan |
| Lead Sponsor | Collaborator |
|---|---|
| ARCA Biopharma, Inc. | Medtronic |
United States, Canada, Hungary, Netherlands, Poland, Serbia,
Aleong RG, Sauer WH, Davis G, Murphy GA, Port JD, Anand IS, Fiuzat M, O'Connor CM, Abraham WT, Liggett SB, Bristow MR. Prevention of atrial fibrillation by bucindolol is dependent on the beta1389 Arg/Gly adrenergic receptor polymorphism. JACC Heart Fail. 2013 Aug;1(4):338-344. doi: 10.1016/j.jchf.2013.04.002. — View Citation
Kao DP, Davis G, Aleong R, O'Connor CM, Fiuzat M, Carson PE, Anand IS, Plehn JF, Gottlieb SS, Silver MA, Lindenfeld J, Miller AB, White M, Murphy GA, Sauer W, Bristow MR. Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation. Eur J Heart Fail. 2013 Mar;15(3):324-33. doi: 10.1093/eurjhf/hfs181. Epub 2012 Dec 7. — View Citation
Liggett SB, Mialet-Perez J, Thaneemit-Chen S, Weber SA, Greene SM, Hodne D, Nelson B, Morrison J, Domanski MJ, Wagoner LE, Abraham WT, Anderson JL, Carlquist JF, Krause-Steinrauf HJ, Lazzeroni LC, Port JD, Lavori PW, Bristow MR. A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11288-93. Epub 2006 Jul 14. — View Citation
O'Connor CM, Fiuzat M, Carson PE, Anand IS, Plehn JF, Gottlieb SS, Silver MA, Lindenfeld J, Miller AB, White M, Walsh R, Nelson P, Medway A, Davis G, Robertson AD, Port JD, Carr J, Murphy GA, Lazzeroni LC, Abraham WT, Liggett SB, Bristow MR. Combinatorial pharmacogenetic interactions of bucindolol and ß1, a2C adrenergic receptor polymorphisms. PLoS One. 2012;7(10):e44324. doi: 10.1371/journal.pone.0044324. Epub 2012 Oct 10. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Time to First Event of Symptomatic Atrial Fibrillation/Atrial Flutter (AF/AFL) or All Cause Mortality (ACM) During the 24-week Follow-up Period After Establishment of Stable Sinus Rhythm (SR) on Study Drug [End of Treatment Week 24]. | Time-to-event is calculated as the date of the event minus the date of initiation of efficacy follow-up, with 1 added in order to include both the start date and end date of the interval. Cox's proportional hazards model will be used to calculate estimated hazard ratios and 95% confidence intervals. The calculations will be performed with the SAS PHREG procedure, with the stratification variables specified in the STRATA statement and the treatment group comparator and any covariates being examined specified in the MODEL statement. For the primary endpoint, the appropriateness of assuming proportional hazards will be explored by the graphing of log (-log(survival function)) over follow-up for each treatment group. | end of treatment week 24 | |
| Secondary | Time to First Event of Symptomatic or Asymptomatic AF/AFL or ACM During the 24-week Follow-up Period After Establishment of Stable SR on Study Drug [End of Treatment Week 24] | Number of days on study medication before participant experienced symptomatic or asymptomatic atrial fibrillation, atrial flutter, or all-cause mortality during the 24 week follow up period. | end of treatment week 24 | |
| Secondary | Number of Patients With Adequate Ventricular Rate Control During the 24-week Follow-up Period | Number of patients with adequate ventricular rate control following the start of medication during the 24-week Follow-up Period | end of treatment week 24 | |
| Secondary | Total Number of Hospitalization Days Per Patient (All-cause) During the Total Study Period (24 Weeks) | Total number of hospitalization days per patient (all-cause) following the start of study medication during the Total Study Period (24 weeks). Hospitalization was defined by a hospital admission (note that same day admit and discharge equates to 0 days duration), ER visits were not counted as events. | 24 weeks |