COMPANION trial

However, the long-term effects of cardiac resynchronization therapy (CRT) on morbidity and mortality were not known. Two clinical trials have established the morbidity and mortality effects of CRT. The COMPANION trial was a three armed trial, testing optimal medical therapy (OPT) against OPT plus CRT by a pacemaker or a OPT plus CRT by an implantable cardioverter-defibrillator (CRT-D) [118]. In this study, patients were enrolled prior to... 

The CARE-HF study was a European study of medical therapy alone versus medical therapy with the addition of a CRT pacemaker [119]. A total of 813 patients were enrolled and randomized in a 1 1 ratio prior to device implant, again a true intent-to-treat design. Patients were followed longer than in the COMPANION trial, for a mean of 29.4 months. The primary end point was the time to... 

Fig. 4.3 Survival in the long-term randomized trials of CRT. In Panel A, the survival in the COMPANION trial was trended to improve by 24% in the cardiac resynchronization therapy (CRT) group P = 0.059), but improved by 36% with CRT with ICD capability (CRT-D). Panel B shows the mortality results from the CARE-HF study. CRT reduced mortality by 36% with a longer follow-up than the COMPANION trial. Note that in both studies, the survival benefit CRT appears to increase with time...

FIGURE 1.5 Summary of evidence supporting defibrillator implantation as stratified by ejection fraction and heart failure class in patients with ischemic cardiomyopathy (A) and nonischemic cardiomyopathy (B). For details of COMPANION trial, see Chapter 5. (CRT, cardiac resynchronization therapy EPS, electrophysiology study NYHA,New York Heart Association.)... 

The Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial was a randomized, open-label, 3-arm... 

Bristow, M.R., A.M. Feldman, and L.A. Saxon, Heart failure management using implantable devices for ventricular resynchronization Comparison of Medical Therapy, Pacing, and Defihrillation in Chronic Heart Failure (COMPANION) trial. COMPANION Steering Committee and COMPANION Clinical Investigators. J Card Fail, 2000. 6(3) p. 276-85. 

Pollard, A.M. (2004). Putting infinity up on trial a consideration of the role of scientific thinking in future archaeologies. In A Companion to Archaeology, ed. Bintliff, J., Blackwell, Oxford, pp. 380-396. 

In this study, CRT reduced the primary endpoint by 37% (hazard ratio 0.63 P < 0.001) and all-cause mortality by 36% (hazard ratio 0.64 P < 0.001). Although the relative risk reduction for mortality at first appears larger than that which trended in COMPANION (24% versus 36%), the mortality benefit was not evident in the early portion of the trial, but the benefit grew over time (see Fig. 4.3). Therefore, much, if not all, of the difference can be attributed to the longer follow-up (29.4 months in CARE-HF versus 14.8-16.5 months in COMPANION). 

Simon R. Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics. Expert opinion on Medical Dignostics (in press). 

Atalay G, Dirix L, Biganzoli L, Beex L, Nooij M, Cameron D, Lohrisch C, Cufer T, Lobelle JP, Mattiaci MR, Piccart M, Paridaens R. The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer a companion study to EORTC Trial 10951, Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients . Ann Oncol 2004 15(2) 211—7. 

Note that the output of roots(p) and eig(compan(p)) each is a complex column vector of length three, i.e., each output lies in C3 and the two solution vectors are identical. Our trial polynomial p(x) = a 3 — 2a 2 + 4 has one pair of complex conjugate roots 1.5652 1.0434 i and one real root -1.1304. The (first row) companion matrix P of a normalized nth degree polynomial p (normalized, so that the coefficient an of xn in p is 1) is the sparse n by n matrix P = C(p) as described in formula (1.2). Note that our chosen p is normalized and has zero as its coefficient ai for a = a 1, i.e., the (1, 2) entry in P is zero. For readers familiar with determinants and Laplace expansion, it should be clear that expanding det(P — xI) along row 1 establishes that our polynomial p(x) is the characteristic polynomial of P. Hence P s eigenvalues are precisely the roots of the given polynomial p. 

Senn SJ (2005b) Cross-over trials. In Everitt BS, Palmer CR (eds). Encyclopaedic Companion to Medical Statistics. Hodder Arnold, London, pp. 88-91. 

Three biomarker types are the most critical, these are surrogate (disease management), stratification (companion), and early detection. The semantics is somewhat confusing as the same types of markers used during a drug trial may have different names compared to the use in clinical practice here the naming used in clinical practice is in parentheses. 

With the publications of the Miracle (1), Miracle ICD (2), COMPANION (3) and CARE-HF (4) trials, biventricular pacing is now an undisputed adjunctive therapy for heart failure, demonstrating an additive symptom and survival benefit over pharmacological therapies alone. Its wider application has been hampered, in part, by the technical challenges of left ventricular lead implantation encountered by the operating physician. (Table 5.1)... 

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