Biology Reference
In-Depth Information
given any type of NSAID in the critical care period because of potential side
effects of bleeding. It is not known if SCI patients could tolerate high doses
immediately after injury, but these studies suggest that NSAIDs should be
the painkillers of choice after SCI patients are stabilized.
3. CLINICAL STUDY WITH CETHRIN
The Cethrin clinical trial was undertaken to assess the safety and tol-
erability of escalating doses of Cethrin ranging from 0.3 to 6 mg in patients
with acute SCI. We chose a noninvasive, fibrin-mediated delivery method
because its use has been supported by experimental studies in rodents (
Guest,
Hesse, Schwab, Bunge, & Bunge, 1997
) and it is used routinely by spinal
surgeons (
Nakamura et al., 2005
). We hypothesized that a single dose of
Cethrin, applied to the dura mater of the injured spinal cord, would be well
tolerated, clinically feasible to administer, and would improve the neurolog-
ical outcome of patients with cervical or thoracic SCI as measured by the
American Spinal Injury Association (ASIA) assessment. Patients with SCI
are in a critically ill state, often fighting for their life, and we chose an inno-
vative noninvasive delivery at the time of decompression surgery to position
Cethrin as a first-line treatment in an acute care setting. The timing of
Cethrin treatment with scheduled surgery was to reduce risk to patients.
Preclinical studies showed that Cethrin was able to penetrate spinal cord
tissue because of the transport sequence (
Lord-Fontaine et al., 2008
).
Cethrin was found to be safe at the doses tested. The treatment-emergent
adverse events that were reported were typical for a population of acute SCI
patients, and no serious adverse events were attributed to the drug (
Fehlings
et al., 2011
). The primary population for efficacy analysis was the intent-to-
treat population that included all patients who were enrolled and received
study medication, and the method of analysis of motor and sensory scores
was of last observation carried forward for patients that dropped out prior
to the 12-month time point.
The patient number in the Cethrin trial was small, and caution needs to be
used in interpreting functional recovery because it was an open-label study.
However, we did observe trends of functional improvement that were prom-
ising. In the 1, 3, and 6 mg dose groups, there was an improvement in motor
function. The lower dose group, the patients treated with 0.3 mg, appears to
show the same recovery as expected from historical control and is likely
because the concentration of the drug is not sufficient for maximum benefit.
On the other end of the dose scale, the 9 mg dose group also did not show any
