DAVID II (Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial II)
DAVID II (Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial II)
The DAVID II Clinical Study evaluates the hypothesis that, in patients needing an ICD but
 without overt indications for pacing, AAI pacing with maximal concomitant drug therapy will
 not increase the rate of the combined endpoint of mortality or hospitalization for new or
 worsened heart failure as compared to patients with ventricular backup pacing.
The DAVID II Clinical Study evaluates the hypothesis that, in patients needing an ICD but
 without overt indications for pacing, AAI pacing with maximal concomitant drug therapy will
 not increase the rate of the combined endpoint of mortality or hospitalization for new or
 worsened heart failure, compared to patients with ventricular backup pacing (VVI), and that
 AAI pacing will result in a reduction of 0.425 years in median event-free survival compared
 to VVI pacing.

 Enrollment and Randomization:

 A total of 600 patients have been enrolled and randomized. All patients previously enrolled
 in the VVI arm of the DAVID Trial who were hemodynamically stable in the VVI-40 programmed
 mode and willing to participate have been randomized in equal numbers into the study. New
 patients (not previously randomized in DAVID) have also been enrolled and similarly
 randomized. The randomization was stratified for investigational site, for previous
 randomization in DAVID vs being newly-enrolled, for a history of CHF, and, among the new
 enrollees, for primary versus preventive eligibility criteria.

 Patients were enrolled with the same indications used in the DAVID Trial, including MADIT II
 indications, with the exception that any patient in class III heart failure must have been on
 optimal heart failure therapy for at least 3 months prior to enrollment and randomization.

 Any planned cardiac surgery (ablation, endocardial resection, valve, aneurysmectomy,
 revascularization) must have been completed before randomization. All patients have received
 commercially available St. Jude dual chamber ICD systems.

 Blinding:

 Patients have not be told to which pacing mode, VVI or AAI they have been assigned (i.e.,
 they will be blinded) in order to reduce the potential for patient generated bias in the
 quality of life assessments which are part of the study.

 Crossover:

 All patients will remain in the study with the device programmed according to their
 randomization assignment, from the point of randomization to the end of follow-up. No
 crossover from one pacing mode to the other is permitted, even after a hospital admission for
 congestive heart failure, until the reason for the requested crossover is reviewed and
 permission is obtained from the University of Washington Clinical Trials Center to change
 pacing mode.

 Optimal CHF Pharmacologic Therapy:

 Optimal CHF Pharmacologic Therapy in the study consists of digoxin, diuretics,
 angiotensin-converting enzyme, (ACE) inhibitors , and beta-blockers. Treatment during the
 study adheres to the Heart Failure Society of America (HFSA) Practice Guidelines. Heart
 Failure symptoms are treated by adjustment of both the rate and rate response of the
 pacemaker and the medications.

 Primary Endpoint:

 The primary endpoint is either death or CHF hospitalization. The determination of CHF
 hospitalization will be made by an Events Committee based on review of the hospital records
 blinded as to treatment arm.

 Secondary endpoints include:

 -  Appropriate ICD therapy--ICD shocks plus Antitachycardia Pacing(ATP)events;

 -  Inappropriate ICD therapy (any therapy deemed not related to Ventricular Tachycardia
 (VT) or Ventricular Fibrillation (VF);

 -  Quality of Life (SF-36, MLHF, VAS)

 Follow-up:

 Patients will be followed at 3-month intervals. The patients are also instructed to call
 their investigational center any time they receive an ICD shock therapy delivery in order to
 have an ICD interrogation/download of the device's memory performed.

 Data Items Collected:

 Standard demographics, clinical histories, and a QoL assessment were obtained at baseline.
 During the follow-up phase, routine clinical data is obtained every 3 months. Quality of life
 assessments are be repeated at 6 months. Events (adverse symptoms, hospitalization,
 death)trigger more extensive data collection including, in particular: 1)all ICD printouts,
 2)detailed hospital records for all CHF hospitalizations, and patient records for all deaths.
Inclusion Criteria:

 I. DAVID I patients enrolled in the VVI-40 who are hemodynamically stable.

 II. Patients with an LVEF 0.40 considered for ICD therapy because of one of the following
 primary, spontaneously occurring, sustained events within the last 6 weeks prior to
 enrollment:

 -  VF arrest (ACC/AHA indication Class 1-1),

 -  VT with syncope (ACC/AHA indication Class 1-1 or 1-2),

 -  Non-syncopal sustained VT with significant cardiac symptoms or BP < 80 (ACC/AHA
 indication Class 1-2, IIb-4),

 OR

 III. Patients considered for ICD therapy because of one of the following:

 -  LVEF < 0.40 with inducible VT or VF within 6 weeks prior to randomization (with or
 without spontaneous arrhythmia), or

 -  LVEF < 0.30 with coronary artery disease, > 1 month from a myocardial infarction, and
 > 3 months from bypass surgery or percutaneous coronary intervention.

 If the ICD was already implanted at time of consideration for enrollment, the device must
 have been programmed in the VVI mode since implant.

 Exclusion Criteria:

 -  NYHA CHF Class III unless on optimal heart failure therapy for at least 3 months prior
 to enrollment,

 -  NYHA CHF Class IV,

 -  Reversible causes of the VT/VF event,

 -  Permanent pacemaker,

 -  First degree AV block with PR interval of more than 240 ms.,

 -  2nd or 3rd or advanced degree heart block,

 -  Symptomatic bradycardia,

 -  Pre-existing endocardial pacing leads,

 -  Permanent atrial fibrillation (>= 6 months or unknown duration),

 -  Patient awaiting a cardiac transplant,

 -  Life expectancy <1 year,

 -  Frequent uncontrolled atrial tachyarrhythmia, or

 -  Inability to obtain informed consent.