Off-Label Use of Recombinant FVIIa: Clinical Characteristics That May Influence Outcomes.

Recombinant activated factor VII (rFVIIa) is increasingly being used in off-label settings. To understand patient characteristics that may affect outcomes in patients who receive off-label rFVIIa, a retrospective review of off-label rFVIIa use from 1/1999 through 3/2005 was conducted at two tertiary-care academic hospitals. Through a hospital IRB-approved protocol, patient charts were examined for all 117 consecutive patients who received off-label rFVIIa. Overall 30-day mortality was 75/117 (64%; 95% CI [0.55 - 0.72]). Overall incidence of new renal dysfunction (serum creatinine>1.3mg/dL for females, >1.5mg/dL for males) or worsening renal dysfunction (>50% increase in creatinine in patients with pre-existing renal dysfunction) was 31/108 (28.7%; 95% CI [0.21 - 0.38]). Thromboembolic complications were documented in 9/117 (7.6%; 95%CI [0.04 - 0.14]). Multiple clinical characteristics were recorded and the Fisher’s exact test was used to determine which characteristics were associated with either an increased (or decreased) frequency of renal dysfunction within 72 hours of rFVIIa administration; or with an increased (or decreased) frequency of 30-day mortality. The characteristics that showed statistically significant association in univariate analysis are listed in the table. The incidence of renal failure was significantly increased over baseline (29%) for patients with either one of 2 characteristics (rows g,h). The incidence of death was significantly increased over baseline (64%) for patients with any of 6 clinical characteristics (a – f) and decreased compared to baseline patients with 3 characteristics (i–k). Characteristics which showed no statistically significant association for either outcomes were: intracranial hemorrhage, subdural hematoma, gastrointestinal bleeding, post-procedural bleeding, trauma, surgical intensive unit, hx of solid tumor, hx of coronary artery disease, hx of atrial fibrillation, hx of diabetes mellitus, gender and age. This analysis helps identify covariant clinical features to be considered when selecting a matched control group to examine patient outcomes resulting from off-label rFVIIa use. | | Patient Clinical Characteristics | n | Renal Dysfunction; Odds Ratio [95% CI] | Death; Odds Ratio [95 % CI] | |:------------------------------------------------------------------------------------------- | ---------------------------------- | -- | -------------------------------------- | --------------------------- | | *p 0.05; ¶One-sided Odds Ratio is reported because no patient survived. | | a | Sepsis | 23 | 0.49 [0.11–1.68]† | >4.73 *,¶ | | b | DIC | 15 | 0.16 [0.004–1.2]† | >2.67 *,¶ | | c | BMT/Stem Cell Transplant | 15 | 0.64 [0.11–2.7]† | >2.67 *,¶ | | d | Heme malignancy | 21 | 0.41 [0.07–1.6]† | 14.9 [2.2–632.6]* | | e | Medical ICU | 36 | 1.2 [0.45–3.2]† | 10.2 [2.8–55.2]* | | f | Pre-existing renal dysfunction | 53 | 0.42 [0.16–1.1]† | 4.7 [1.8–12.7]* | | g | Liver disease/Ped liver transplant | 23 | 3.19 [1.02–9.78]** | 0.54 [0.19–1.5]† | | h | Cardiac/thoracic surgery | 18 | 3.1 [0.95–9.9]** | 0.86 [0.28–2.9]† | | i | Anticoagulant-related bleeding | 19 | 0.64 [0.11–2.7]† | 0.19 [0.06–0.62]* | | j | Surgical prophylaxis | 6 | 0.48 [0.01–4.6]† | 0 [0–0.32]* |