Atrial Fibrillation
Conditions
Brief summary
The purpose of this study is to demonstrate that the amount of effective CRT (Cardiac Resynchronization Therapy) pacing during AF (atrial fibrillation) when CAFRPlus (Conducted AF Response Plus) is applied is not inferior to the amount of effective CRT pacing during AF when CAFR (Conducted AF Response) is applied.
Detailed description
The CRTee study is an IDE, prospective, multi-center, randomized, controlled, crossover clinical study, conducted worldwide and designed to demonstrate that the amount of effective CRT pacing during AF (atrial fibrillation) when CAFRPlus (Conducted AF Response Plus) is applied is not inferior to the amount of effective CRT pacing during AF when CAFR (Conducted AF Response) is applied. The study will be conducted at up to 30 centers located in the United States, Europe and Middle East and Africa (MEA).
Interventions
DEVICEConducted AF Response (CAFR)
The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.
DEVICEConducted AF Response Plus (CAFRPlus)
The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is willing to sign and date the study patient Informed Consent form. * Subject is at least 18 years of age (or older, if required by local law). * Subject is expected to remain available after enrollment to complete follow-up visits in both arms of the study * Subject has had a Medtronic Viva or Brava CRT-D device implanted at least 30 days prior to enrollment. * Subject has history of AF burden, of at least 6 days of at least 4 hours of AF over any 4 week period within the last 90 days as documented in device diagnostic data OR if subject has no atrial lead (therefore no device diagnostic data) but clinical evidence of high AF burden. * Subject has demonstrated history of being able to complete Left Ventricular Capture Management (LVCM) documented in device data. * Subject has a documented % V pacing during AF of less than or equal to 97% within 90 days prior to enrollment or within 10 days after enrollment.
Exclusion criteria
* Subject has undergone AV node ablation for treatment of AF. * Subject has complete or 3rd degree AV block. * Subject has had an MI within 30 days. * Subject has medical conditions that limit study participation (per physician discretion). * Subject is enrolled in one or more concurrent studies that could confound the study results as determined by Medtronic. * Subject has a limited life expectancy for non-cardiac causes that would not allow completion of the study. * Subject is pregnant (in the US, all women of child-bearing potential must undergo a pregnancy test within seven days prior to CRTee download). * Subject meets the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Effective CRT Pacing During AF (Non-inferiority Test) | Up to 4 months | The primary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is not inferior to when CAFR is applied (non-inferiority test). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Effective CRT Pacing During AF (Superiority Test) | Up to 4 months | The secondary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is greater than when CAFR is applied (superiority test). |
Countries
Hungary, Italy, Saudi Arabia, Slovakia, South Africa, United Kingdom, United States
Participant flow
Recruitment details
A total of 71 subjects were enrolled from 22 investigational centers in the United States, Europe and Middle East. The first subject was enrolled on 07 Oct 2014, and last enrollment was on 08 Jan 2016.
Pre-assignment details
Of the 71 enrolled subjects, 5 did not meet eligibility criteria (AV node ablation - 2, complete heart block - 3) and were exited from the study prior to randomization assignment.
Participants by arm
| Arm | Count |
|---|---|
| Group A: CAFR First Subjects randomized to Group A will receive CAFR first, then cross over to CAFRPlus.
Conducted AF Response (CAFR): The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.
Conducted AF Response Plus (CAFRPlus): The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing. | 33 |
| Group B: CAFRPlus First Subjects randomized to Group B will receive CAFRPlus first, then cross over to CAFR.
Conducted AF Response (CAFR): The CAFR algorithm is currently available in the Medtronic market-released devices and intended to promote delivery of CRT pacing during conducted AT/AF episodes.
Conducted AF Response Plus (CAFRPlus): The CAFRPlus algorithm is part of the CRTee feature set. This feature set has a diagnostic element that tracks the loss of effective CRT pacing that is occurring over time, both during normal sinus rhythm (NSR) and during AF. It also has an interventional element (i.e. CAFRPlus) that uses this evaluation of effective CRT pacing to adjust the pacing rate during AF to decrease loss of effective CRT pacing. | 33 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Eligibility criteria not met | 0 | 3 |
Baseline characteristics
| Characteristic | Group A: CAFR First | Group B: CAFRPlus First | Total |
|---|---|---|---|
| Age, Continuous | 70.7 years STANDARD_DEVIATION 11.6 | 72.4 years STANDARD_DEVIATION 9.1 | 71.6 years STANDARD_DEVIATION 10.4 |
| Gender Female | 4 Participants | 1 Participants | 5 Participants |
| Gender Male | 29 Participants | 32 Participants | 61 Participants |
| Region of Enrollment Hungary | 4 participants | 4 participants | 8 participants |
| Region of Enrollment Italy | 5 participants | 4 participants | 9 participants |
| Region of Enrollment Saudi Arabia | 5 participants | 4 participants | 9 participants |
| Region of Enrollment Slovakia | 2 participants | 1 participants | 3 participants |
| Region of Enrollment United Kingdom | 3 participants | 3 participants | 6 participants |
| Region of Enrollment United States | 14 participants | 17 participants | 31 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 71 |
| serious Total, serious adverse events | 7 / 71 |
Outcome results
Primary
Percentage of Effective CRT Pacing During AF (Non-inferiority Test)
The primary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is not inferior to when CAFR is applied (non-inferiority test).
Time frame: Up to 4 months
Population: Randomized subjects who had paired measurements available from both CAFR period and CAFRPlus period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAFR ON | Percentage of Effective CRT Pacing During AF (Non-inferiority Test) | 80.8 percentage of effective CRT pacing | Standard Deviation 14.3 |
| CAFRPlus ON | Percentage of Effective CRT Pacing During AF (Non-inferiority Test) | 87.8 percentage of effective CRT pacing | Standard Deviation 7.8 |
Comparison: Null Hypothesis (Ho): μd ≤ -2% Alternative Hypothesis (Ha): μd \> -2% where μd is the paired difference in percent effective CRT pacing during AF between when CAFRPlus is applied and when CAFR is applied, based on subjects' paired measurements from the two cross-over follow-up periods, and -2% is the non-inferiority margin selected based upon clinical judgment.p-value: <0.000195.86% CI: [4.5, 9.5]t-test, 1 sided
Secondary
Percentage of Effective CRT Pacing During AF (Superiority Test)
The secondary objective is to demonstrate that the percent effective CRT pacing during AF when CAFRPlus is applied is greater than when CAFR is applied (superiority test).
Time frame: Up to 4 months
Population: Randomized subjects who had paired measurements available from both CAFR period and CAFRPlus period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAFR ON | Percentage of Effective CRT Pacing During AF (Superiority Test) | 80.8 percentage of effective CRT pacing | Standard Deviation 14.3 |
| CAFRPlus ON | Percentage of Effective CRT Pacing During AF (Superiority Test) | 87.8 percentage of effective CRT pacing | Standard Deviation 7.8 |
Comparison: Null Hypothesis (Ho): μd ≤ 0% Alternative Hypothesis (Ha): μd \> 0% where μd is the paired difference in percent effective CRT pacing during AF between when CAFRPlus is applied and when CAFR is applied, based on subjects' paired measurements from the two cross-over follow-up periods.p-value: <0.000195.86% CI: [4.5, 9.5]t-test, 1 sided