Clinical Trial: Methods and Design
Rationale and Design of the Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy Study (LAPTOP-HF)

https://doi.org/10.1016/j.cardfail.2015.04.012Get rights and content

Highlights

  • Measurements of left atrial pressure (LAP) to guide medical therapy may prevent decompensated HF.

  • LAPTOP-HF is a prospective, multicenter, randomized trial of patients with NYHA III symptoms.

  • It assesses the safety and efficacy of physician-directed patient self-management strategy with the use of LAP.

  • LAPTOP-HF will provide key data on implantable LAP monitoring and a new HF treatment paradigm.

Abstract

Background

Daily measurements of left atrial pressure (LAP) may be useful for guiding adjustments in medical therapy that prevent clinical decompensation in patients with severe heart failure (HF).

Study Design

LAPTOP-HF is a prospective, multicenter, randomized, controlled clinical trial in ambulatory patients with advanced heart failure in which the safety and clinical effectiveness of a physician-directed patient self-management therapeutic strategy based on LAP measured twice daily by means of an implantable sensor will be compared with a control group receiving optimal medical therapy. The trial will enroll up to 730 patients with New York Heart Association functional class III symptoms and either a hospitalization for HF during the previous 12 months or an elevated B-type natriuretic peptide level, regardless of ejection fraction, at up to 75 investigational centers. Randomization to the treatment group or control group will be at a 1:1 ratio in 3 strata based on the ejection fraction (EF > or ≤35%) and the presence of a de novo CRT device indication.

Summary

LAPTOP-HF will provide essential information about the role of implantable LAP monitoring in conjunction with a new HF treatment paradigm across the spectrum of HF patients.

Section snippets

Overview

LAPTOP-HF is a prospective, multicenter, randomized, controlled clinical trial in ambulatory patients with advanced HF that will evaluate the safety and clinical effectiveness of implanted LAP monitoring systems linked with a physician-directed patient self-management therapeutic strategy. The trial will enroll up to 730 patients with NYHA functional class III symptoms and either a hospitalization for HF during the previous 12 months or an elevated B-type natriuretic peptide (BNP) level of ≥400

LAPTOP Monitoring Systems

Two implantable LAP monitoring systems (Fig. 1) manufactured by St Jude Medical (Sylmar, California) will be used depending on clinical indications and the implanter’s discretion. A stand-alone system includes a HeartPOD implantable sensor lead (ISL) that measures the LAP waveform, core temperature, and the intracardiac electrogram (IEGM). The ISL is coupled to an implantable communications module (ICM), which communicates the measured signals to an external radiofrequency (RF) source/reader.

Subjects and Randomization

Subjects meeting the inclusion/exclusion criteria (Table 1) and giving informed consent will be randomized in a 1:1 ratio into the treatment and control groups. The trial will enroll up to 730 patients at up to 75 centers. Randomization will be stratified 3 ways as indicated in Table 2.

Stratum 1 includes subjects with a baseline LVEF ≤35% and no new indication for CRT per American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society/European Society of Cardiology

Study Procedures and Follow-up

An experienced proctor will be present at each new implanting physician's initial procedures to assure adequate training and compliance with the protocol until both the sponsor and physician consider that it is no longer necessary. To provide training in the use of the Web-based software and achieve compliance with the protocol treatment group prescribing guidelines, Web-based LAP system technical assistance rounds are done with each site. Technical issues with patients from both treatment and

Study End Points

The primary safety end point is freedom from study-related major adverse cardiovascular and neurologic events (MACNE) in the treatment group at 12 months. The primary effectiveness end point is the reduction in the relative risk of HF hospitalization, including ADHF and complications of HF treatment such as hypotension and acute renal failure.

Secondary end points include (1) noninferiority analysis of the relative risk of all-cause MACNE (safety) and (2) days alive and out of hospital for HF

Power Calculation and Statistical Analyses

The sample size was calculated under the following assumptions: (1) the event rate for HF hospitalization in the control group is 0.6 per patient per year, (2) relative risk reduction of HF-related hospitalizations in the Treatment group over the control group is 25%, and (3) withdrawal rate is 25% at 12 months. For 80% power at a 5% significance level, 624 events are required. The number of patients needed to enroll is a maximum of 730.

The power calculation for the primary safety end point

Monitoring

The Steering Committee in collaboration with the sponsor developed the study protocol and is responsible for monitoring its implementation. The independent Clinical Events Committee (CEC) adjudicates the cardiac and noncardiac events that qualify as an end point. The CEC includes physicians with expertise in clinical trials, cardiovascular diseases, and statistics. Source documentation for events considered for the primary effectiveness end point is redacted to blind for study group assignment.

Discussion

Implantable hemodynamic monitoring has been developed for outpatient HF management with the goal of improving outcomes by reducing episodes of decompensation, providing adjunctive information to patients that could promote adherence to diet and lifestyle management and assist in the titration of standard medical therapy to optimally tolerated dosages. Previous studies have suggested that management of ambulatory hemodynamics may improve outcomes in patients with advanced chronic HF.10, 19, 20,

Disclosures

This trial is sponsored by St Jude Medical. Drs Mathew S. Maurer, Phil Adamson, Marc Klapholz, Leslie Saxon, Jagmeet P. Singh, and William T. Abraham are on the LAPTOP-HF Steering Committee and receive financial compensation for this activity. Dr Michael R. Gold is a consultant and does clinical trials for St Jude Medical, Boston Scientific, and Medtronic and is on the LAPTOP-HF Steering Committee. Dr Richard Troughton is on the LAPTOP Steering Committee and receives grant funding from St Jude

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