A Randomized, Open-Label, Single-Dose, Small Study to Evaluate the Safety and Effectiveness of Hydromorphone in Patients With Short Term, Moderate to Severe Postoperative Pain
A Randomized, Open-Label, Single-Dose, Small Study to Evaluate the Safety and Effectiveness of Hydromorphone in Patients With Short Term, Moderate to Severe Postoperative Pain
The purpose of this small study was to investigate the safety and effectiveness of OROS
 hydromorphone HCI for the treatment of short-term, moderate to severe postoperative pain
 following total knee replacement surgery.
This was a multicenter, randomized (patients are assigned different treatments based on
 chance), open-label, single dose small study. During the 36 hour study period, concomitant
 analgesic (pain) medications and physical therapy were recorded in the patient's case report
 form. The study duration for each patient was 36 hours after a single dose of OROS
 hydromorphone HCI had been administered. After surgery, eligible patients had to tolerate
 liquids, swallow a tablet, and have audible bowel sounds. Before OROS hydromorphone HCI was
 administered, all analgesic medications were discontinued and patients with a pain score of
 2(moderate pain) or 3 (severe pain) upon movement were eligible to enter the study and
 receive a single oral dose of OROS hydromorphone HCI. Patients had to have stable heart
 rates, blood pressure, respiration, oxygen saturation greater than or equal to 94% and
 patients who had undergone regional anesthesia had to have motor and sensory recovery from
 nerve blockade. Qualifying patients were given OROS hydromorphone HCI between 6 and 48 hours
 after completion of the surgical procedure. Patients were randomized into 3 groups (OROS
 hydromorphone HCI 8, 16, and 32 mg). The precise time of OROS hydromorphone HCI
 administration was considered time zero. To maintain consistency, dosing was to occur between
 6 am and 2 pm, if possible. Following study drug administration, patients could be given
 rescue medication of oral hydromorphone immediate-release tablets (2 or 4 mg) for
 breakthrough pain as needed. Oxygen saturation, vital signs, pain relief ratings, and pain
 intensity ratings at rest and upon movement were obtained at 2-hour time intervals during the
 first 8 hours following study drug administration, and at 4 hour intervals from 8 to 36 hours
 following study drug administration. The study concluded 36 hours after dosing, at which time
 a global evaluation of pain relief was obtained from each patient. One single dose of OROS
 hydromorphone HCI (8, 16, or 32 mg) administered orally at the beginning of the 36 hour
 study.
Inclusion Criteria:

 -  Patients undergoing primary, unilateral total knee replacement surgery where use of
 opioid analgesics for short-term postoperative pain is required

 -  At baseline must be able to tolerate oral liquids, swallow a tablet, and have the
 presence of bowel sounds upon examination

 -  Patients must demonstrate stable vital signs immediately before dosing with OROS
 hydromorphone HCI

 -  At baseline pain intensity upon movement must be scored by the patient as 2 or 3
 (moderate or severe) on the Pain Intensity Rating Scale

 -  At baseline patients receiving regional anesthetics/analgesics must demonstrate
 recovery from the motor and sensory effects of the nerve blockade

 -  Patients must be administered OROS hydromorphone HCI between 6 and 48 hours following
 completion of surgery

 -  Patients should expect to remain hospitalized for 36 hours after study drug
 administration.

 Exclusion Criteria:

 -  Patients either intolerant of hydromorphone or who have experienced an anaphylactic
 IgE-mediated immune response (e.g. hives, wheezing, angioedema or bronchospasms) to
 any opioid agonist

 -  Patients having previously undergone the following major surgery for high tibial
 osteotomy, knee arthroplasty to the affected knee

 -  Patients with any gastrointestinal disorder, including pre-existing severe GI
 narrowing (pathologic or iatrogenic) that may affect the absorption or transit of
 orally administered drugs

 -  Patients who are pregnant or breast-feeding. A negative pregnancy test is required
 prior to administration of the study medication in females of childbearing potential

 -  Patients with significant CNS disorder, including but not limited to head injury,
 intracranial lesion, increased intracranial pressure, seizure disorder, stroke within
 the past 6 months, and disorders of cognition

 -  Patients with clinically significant impaired renal, hepatic, or hematological
 function

 -  adrenocortical insufficiency

 -  uncontrolled hypothyroidism or hyperthyroidism, or clinically significant urinary
 obstruction