Trial Outcomes & Findings for Multimodal Pain Management After Robotic-Assisted Total Laparoscopic Hysterectomy (NCT NCT04429022)

Results Overview

Total opioid pain medications required 0-3h post op in morphine milligram equivalents (MME)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

68 participants

Primary outcome timeframe

0-3 hours after surgery

Results posted on

2023-08-01

Participant Flow

For the intervention arm, patients were recruited from November 24, 2020 to May 24, 2022. Data for the retrospective controls who underwent their hysterectomy from 11/27/2018 to 12/12/2019, was obtained via chart review. This was a prospective cohort study with retrospective controls. To allow for adjustment to this new protocol, 11 months were allocated to the institution and staff, prior to enrolling patients in the intervention arm.

49 patients were analyzed as 18 of 28 intervention arm participants did not receive the intervention or their care required deviation from the from study protocol (e.g., no minimally invasive hysterectomy due to laparotomy, no paracervical block due to indocyanine green injection for lymph node mapping, no postoperative protocol medications due to limited resources and logistical issues). One of the 40 control participants was excluded due to uterine weight exceeding the study protocol range.

Participant milestones

Participant milestones
Measure	Prospective Cohort Pre-Op: * Gabapentin 600mg PO x 1 and * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with 0.5% ropivacaine; 10 mL bilaterally (2 points), total of 20mL * 0.5% ropivacaine subcutaneous injection at all laparoscopic port sites; another 10mL * Operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME). If patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Overall Study STARTED	28	40
Overall Study COMPLETED	10	39
Overall Study NOT COMPLETED	18	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Prospective Cohort Pre-Op: * Gabapentin 600mg PO x 1 and * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with 0.5% ropivacaine; 10 mL bilaterally (2 points), total of 20mL * 0.5% ropivacaine subcutaneous injection at all laparoscopic port sites; another 10mL * Operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME). If patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Overall Study Protocol Violation	18	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient	Total n=49 Participants Total of all reporting groups
Age, Continuous	44.60 years n=10 Participants	44.13 years n=39 Participants	44.37 years n=49 Participants
Sex: Female, Male Female	10 Participants n=10 Participants	39 Participants n=39 Participants	49 Participants n=49 Participants
Sex: Female, Male Male	0 Participants n=10 Participants	0 Participants n=39 Participants	0 Participants n=49 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	10 participants n=10 Participants	39 participants n=39 Participants	49 participants n=49 Participants

PRIMARY outcome

Timeframe: 0-3 hours after surgery

Total opioid pain medications required 0-3h post op in morphine milligram equivalents (MME)

Outcome measures

Outcome measures
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Total Opioid Pain Medications Required 0-3h Post op in Morphine Milligram Equivalents (MME)	2.00 morphine milligram equivalents (MME) Interval 0.0 to 8.0	5.32 morphine milligram equivalents (MME) Interval 0.0 to 17.5

PRIMARY outcome

Timeframe: 3-24 hours after surgery

Total opioid pain medications required through 3-24h post op in MME

Outcome measures

Outcome measures
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Total Opioid Pain Medications Required Through 3-24h Post op in MME	.20 morphine milligram equivalents (MME) Interval 0.0 to 2.0	12.27 morphine milligram equivalents (MME) Interval 0.0 to 52.0

SECONDARY outcome

Timeframe: 3-24 hours after surgery

Subjective, Score 0-10 with 0 being no pain and 10 being severe pain

Outcome measures

Outcome measures
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Pain Scores	1.75 score on a scale Interval 0.0 to 6.0	5.43 score on a scale Interval 0.0 to 8.0

SECONDARY outcome

Timeframe: 0-3 hours after surgery

Subjective, Score 0-10 with 0 being no pain and 10 being severe pain

Outcome measures

Outcome measures
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Pain Scores	3.82 score on a scale Interval 0.0 to 8.0	5.13 score on a scale Interval 0.0 to 9.0

SECONDARY outcome

Timeframe: 0- 240 hours

Length of stay in hours

Outcome measures

Outcome measures
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Length of Stay in Hours	12.05 hours Interval 6.0 to 34.0	35.82 hours Interval 10.0 to 239.0

SECONDARY outcome

Timeframe: 0-14 days

Number of patients with return to the clinic, emergency department due to post operative pain within a 2 week period

Outcome measures

Outcome measures
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Number of Patients With Return to the Clinic, Emergency Department Due to Post Operative Pain Within a 2 Week Period	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 0-300 minutes

minutes

Outcome measures

Outcome measures
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Operative Time	128.80 minutes Interval 90.0 to 179.0	139.69 minutes Interval 73.0 to 262.0

SECONDARY outcome

Timeframe: 0-300 minutes

milliliters (mL)

Outcome measures

Outcome measures
Measure	Prospective Cohort n=10 Participants Pre-Op: * Gabapentin 600mg PO PO x 1 prior to surgery (in pre-op) * Acetaminophen 1000mg PO x1 prior to surgery (in pre-op) Intra-Op: * Paracervical block with local anesthetic (0.5% ropivacaine); 10 mL bilaterally (2 point) for total of 20mL * Local anesthetic (0.5% ropivacaine) at all laparoscopic port sites; another 10mL * Will operate at \<15mmHg intra-abdominal pressure, with goal of \<12mmHg * At end of procedure during closure of fascia, give 30mg ketorolac IV x 1 Post-Op: * Gabapentin 300mg PO BID for 7 days * Acetaminophen 1000mg PO q6h x 2 days then 1000mg q6h PRN * Celecoxib 200mg PO q 12h x 7d * Dilaudid 1mg IV PRN q3h while inpatient; oxycodone 12 x 5mg upon discharge (90MME) if patient did not use any opioids postoperatively while inpatient, will not prescribe opioid medication upon discharge	Historical Control n=39 Participants Traditional post-operative opioid medication regimen: Dilaudid 1mg IV PRN q3h while inpatient; Percocets 12 x 5mg/325 (90MME) upon discharge Hydromorphone: 1mg IV PRN q3h, post op, while inpatient
Estimated Blood Loss	63.50 milliliters Interval 10.0 to 150.0	58.46 milliliters Interval 5.0 to 200.0

Adverse Events

Prospective Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Historical Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Sarah Andres, PI

University at Buffalo

Phone: 7163230631

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place