Pain, Postoperative
Conditions
Keywords
live kidney donor, donor nephrectomy
Brief summary
The investigators will assess how the use of toradol and pregabalin affects return to bowel function and see if there is a difference in length of hospital stay. Narcotic use can affect bowel function so the investigators hypothesize that use of Toradol will decrease delayed bowel function and aid in a patients discharge and reduction of hospital stay.
Detailed description
Perioperative pain management is a significant challenge following surgery. Many pathways contribute to perioperative pain, including nociceptive, inflammatory, and neuropathic sources. Although opioids have long been a mainstay for perioperative analgesia, other non-opioid therapies have been increasingly used as part of a multimodal analgesic regimen to provide improved pain control while minimizing opioid-related side effects TORADOL (ketorolac tromethamine), is a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days in adults), management of moderately severe acute pain that requires analgesia at the opioid level. Anecdotal evidence has shown that the use of Toradol (Ketorolac) is safe in renal surgery patients. The study team aims to further evaluate this in a pilot study specifically in the population of patient who have donated their kidney in live kidney transplants. The study team will assess how the use of toradol affects return to bowel function and see if there is a difference in length of hospital stay. Narcotic use can affect bowel function so the investigators hypothesize that use of Toradol will decrease delayed bowel function and aid in a patients discharge and reduction of hospital stay. The study team will assess differences in visual analog pain scores and total narcotic consumption, whereas secondary endpoints of urine output, serum creatinine and hemoglobin levels to assess for efficacy and safety. Pregabalin is prescribed for neuropathic pain. In many studies, preoperative administration of pregabalin reduced postoperative morphine consumption and early postoperative pain. There will be two arms of the study including: Arm 1 (pure placebo group): Placebo oral preop then Saline placebo IV x 1 in the OR, then saline placebo IV every 6 hours for 7 doses. Arm 2: Pregabalin 75mg oral preop, then Ketorolac 30 mg IV x 1 in the OR, then ketorolac 15 mg IV every 6 hours for 7 doses. Toradol and Lyrica will be used consistent with its FDA approval in terms of dosing, route of administration, etc.
Interventions
DRUGKetorolac
Ketorolac was administered intravenously: 30 mg in the operating room, and 15 mg every 6 hours for 7 doses post-operatively.
DRUGPregabalin
Pregabalin was administered orally: 75 mg 30 minutes prior to operation.
DRUGPlacebo oral capsule
Placebo oral capsule was administered orally 30 minutes prior to operation.
DRUGSaline
Saline was administered intravenously: once in the operating room, and every 6 hours for 7 doses post-operatively.
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients anticipating donating a kidney in a live kidney donor transplant.
Exclusion criteria
* Patients not receiving a donor nephrectomy * Pregnant, lactating, or nursing mothers * Medical allergies or history that would otherwise be contraindicated for of a non-steroidal anti-inflammatory drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Narcotic Use | 82.25 hours | Cumulative narcotic use was defined by cumulative morphine equivalents over the course of a patient's hospital course. The Washington State Agency Medical Director's Group Opioid dose calculator was used to provide a total morphine dose equivalent (MDE) for each patient while in the hospital. |
| Length of Hospital Stay | 82.25 hours | Primary outcomes include length of hospital stay (LOS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Creatinine Levels at One Year Post-operatively | 1 year | Renal function was evaluated by following serum creatinine levels for up to one year post-operatively. |
| Bleeding Risk | 24 hours | Hematocrit levels were evaluated post-operatively for up to a day post-operatively for signs of blood loss. |
| Number of Patients With Urinary Retention | 82.25 hours | Patients were evaluated post-operatively during hospital stay for instances of urinary retention. |
| 30 Day Mortality | 30 days | Primary outcomes include 30 day mortality post-operatively. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Toradol and Lyrica Over-Encapsulated Pregabalin 75 mg was administered PO 30 minutes prior to operation; Ketorolac 30 mg IV x 1 was administered in the OR, followed by ketorolac 15 mg IV every 6 hours for 7 doses (or until discharge).
Ketorolac: Ketorolac was administered intravenously: 30 mg in the operating room, and 15 mg every 6 hours for 7 doses post-operatively.
Pregabalin: Pregabalin was administered orally: 75 mg 30 minutes prior to operation. | 33 |
| Placebo and Standard of Care Identical placebo oral capsule (same size and color) was administered PO 30 minutes prior to operation; Saline placebo IV x 1 was administered in the OR, followed by saline placebo IV every 6 hours for 7 doses. Standard of care practices maintained.
Placebo oral capsule: Placebo oral capsule was administered orally 30 minutes prior to operation.
Saline: Saline was administered intravenously: once in the operating room, and every 6 hours for 7 doses post-operatively. | 29 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Data could not be validated | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo and Standard of Care | Total | Toradol and Lyrica |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 59 Participants | 32 Participants |
| Age, Continuous | 45.1 years STANDARD_DEVIATION 12.2 | 44.4 years STANDARD_DEVIATION 11.4 | 43.8 years STANDARD_DEVIATION 11 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 17 Participants | 42 Participants | 25 Participants |
| Sex: Female, Male Male | 12 Participants | 20 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 29 |
| other Total, other adverse events | 0 / 32 | 0 / 29 |
| serious Total, serious adverse events | 0 / 32 | 0 / 29 |
Outcome results
Primary
Cumulative Narcotic Use
Cumulative narcotic use was defined by cumulative morphine equivalents over the course of a patient's hospital course. The Washington State Agency Medical Director's Group Opioid dose calculator was used to provide a total morphine dose equivalent (MDE) for each patient while in the hospital.
Time frame: 82.25 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toradol and Lyrica | Cumulative Narcotic Use | 27 mg |
| Placebo and Standard of Care | Cumulative Narcotic Use | 45 mg |
p-value: 0.006Wilcoxon (Mann-Whitney)
Primary
Length of Hospital Stay
Primary outcomes include length of hospital stay (LOS).
Time frame: 82.25 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toradol and Lyrica | Length of Hospital Stay | 51.5 hours |
| Placebo and Standard of Care | Length of Hospital Stay | 57.3 hours |
p-value: 0.029Exact Wilcoxon rank sum test
Secondary
30 Day Mortality
Primary outcomes include 30 day mortality post-operatively.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Toradol and Lyrica | 30 Day Mortality | 0 Participants |
| Placebo and Standard of Care | 30 Day Mortality | 0 Participants |
Secondary
Bleeding Risk
Hematocrit levels were evaluated post-operatively for up to a day post-operatively for signs of blood loss.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Toradol and Lyrica | Bleeding Risk | 6.3 percentage of hematocrit | Standard Deviation 2.1 |
| Placebo and Standard of Care | Bleeding Risk | 4.3 percentage of hematocrit | Standard Deviation 2.5 |
p-value: 0.002t-test, 2 sided
Secondary
Number of Patients With Urinary Retention
Patients were evaluated post-operatively during hospital stay for instances of urinary retention.
Time frame: 82.25 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Toradol and Lyrica | Number of Patients With Urinary Retention | 1 Participants |
| Placebo and Standard of Care | Number of Patients With Urinary Retention | 0 Participants |
p-value: >0.99Fisher Exact
Secondary
Serum Creatinine Levels at One Year Post-operatively
Renal function was evaluated by following serum creatinine levels for up to one year post-operatively.
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toradol and Lyrica | Serum Creatinine Levels at One Year Post-operatively | 0.6 mg/dL |
| Placebo and Standard of Care | Serum Creatinine Levels at One Year Post-operatively | 0.7 mg/dL |
Comparison: The safety outcome was used to power our study.To achieve 90% power at a 2.5% significance level for testing that the post-surgery creatinine increase is at most two-fold (where 1.5 fold is expected), or alternatively for the pre-surgery creatinine group to be ≥0.5 times the post-surgery, we need 17 subjects in the toradol group. This calculation was based on a non-inferiority test (one sided t-test) using a coefficient of variation of 0.25 based on preliminary data.p-value: <0.0001Wilcoxon (Mann-Whitney)