• Cardiology Clinical Trials
• Heart Failure

• Cardiology Clinical Trials
• Heart Failure
• Cardiology

Gerhard Hindricks, MD, University of Leipzig, Heartcenter, Leipzig, Germany, discussed results from the Influence of Home Monitoring on the Clinical Status of Heart Failure Patients With an Impaired Left Ventricular Function trial [IN-TIME; NCT00538356], a randomized controlled trial that demonstrated a significant improvement in a composite of heart failure (HF) status and clinical events by using implant-based remote-monitoring to assist physicians in the management of patients with advanced HF.

The ability to more closely monitor these tenuous patients has long been hypothesized as a way to improve a wide variety of HF endpoints. Certain clinical events or characteristics, such as arrhythmia or increased heart rate at rest, may precipitate worsening HF, leading to hospital admission or death [Opasich C et al. Am J Cardiol 2001]. Home-monitoring (HM) data provides access to these early predictive changes of worsening HF and thereby may enable intervention prior to hospitalization [Sack S et al. Eur J Heart Fail 2011].

IN-TIME was designed to evaluate the impact of physician access to these predictive parameters (eg, heart rate, atrial fibrillation burden) in relative “realtime” to influence changes in therapeutic treatment. No specific guidance was provided to physicians; treatment decisions were left to each physician's clinical judgment. The primary endpoint was the modified Packer score—a clinical composite score based on mortality, overnight hospitalization for worsening HF, NYHA class status, and changes in the patient's global self-assessment score. Secondary endpoints included all-cause total mortality and the number of overnight hospitalizations due to worsening HF.

The trial was conducted among 36 international investigational centers. Inclusion criteria included a history of HF ≥3 months, NYHA Class II or III symptoms for 1 month prior to screening, left ventricular ejection fraction ≤35% within 3 months prior to screening, indication for diuretic therapy and an indication for an implantable cardioverter defibrillator (ICD; with or without cardiac resynchronization therapy). All patients received a device with remote-monitoring capability at the time of ICD implantation. Although remote monitoring data were collected for all patients, these were not available to treating physicians until the study was completed in the control group.

Of the 716 patients enrolled, 52 were excluded during an initial run-in; 664 were subsequently randomized to either HM (n=333) or a control group with standard HF care (n=331). Baseline characteristics were similar in both arms, except for a slightly lower utilization of angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker in the control arm (86.4% vs 92.2%). A total of 82 patients (30 in the HM arm and 52 in the control arm) did not complete 12 months of follow-up. This difference was primarily related to the excess of mortality in the control arm compared to HM arm (control 27 vs HM 10).

At 12 months, significantly fewer patients in the HM group compared with the control group had reached the primary endpoint, worsening of HF according to modified Packer score (18.9% vs 27.5%; p<0.05). A significantly reduced rate was found in the secondary endpoint of all-cause mortality (HR, 0.36; 95% CI, 0.17 to 0.74; p=0.004). The increase in mortality was largely cardiovascular in cause (HR, 0.37; 95% CI, 0.16 to 0.83; p=0.012).

IN-TIME has contributed important data regarding the efficacy of telemonitoring in patients with HF. Further analyses are needed to better understand its impact on how physicians responded to these data and the consequent changes in conventional therapies. Prof. Hindricks summarized by stating that IN-TIME is the first implant-based, telemonitoring, randomized trial to show significant survival benefits of this type of monitoring in advanced HF patients. The decrease in mortality will require further studies for validation since there were a small number of deaths (37 total) in this trial, and it was not powered to evaluate this endpoint.

• © 2013 MD Conference Express®