Spinal Morphine or Intravenous Lidocaine in Robot-assisted Upper Urologic Surgery (SMILe)

SMILe: Spinal Morphine or Intravenous Lidocaine in Robot-assisted Upper Urologic Surgery

The goal of this clinical trial is to learn whether the addition of spinal analgesia leads to superior recovery in patients undergoing robotic-assisted laparoscopic upper urinary tract surgery under general anesthesia. The main questions it aims to answer are:

• Is the decrease in wellbeing as quantified by the patient-centered outcome scale "Quality of Recovery 15" (QoR-15), from baseline to the first day after surgery (POD 1), at least 8.0 points less in patients receiving spinal analgesia in addition to general anesthesia?
• Does spinal analgesia result in improved recovery as quantified by QoR-15 at POD 7, the incidence of postoperative pain at rest and at mobilization, nausea and vomiting, the need for opioid analgesics, time out-of-bed, length of stay and the incidence of complications?
• Does spinal analgesia increase workload in the OR, as quantified by time from arrival in the OR to start of surgery?
• Does spinal analgesia result in an increased incidence of hypotension and cardiac dysfunction during surgery, as well as an increased incidence of pruritus after surgery?

Participants will be randomized to receive either spinal analgesia with bupivacaine and morphine preoperatively or an intravenous infusion with lidocaine intraoperatively.

QoR-15 and other markers of recovery will be registered using structured interviews preoperatively, at POD1 and POD7. In addition, patients will record pain at rest and at mobilization three times daily in a diary.

In a subgroup of patients advanced hemodynamic parameters will be recorded using pulse-contour analysis before, during and after surgery. Blood samples will also be collected in these patients at fixed intervals and analyzed for amongst others inflammation and cardiac dysfunction.

Study Overview

• Status: Recruiting
• Conditions: Renal Cancer; Ureter Cancer; Other Specified Disorders of Kidney and Ureter; Benign Neoplasm of Ureter; Calculus of Kidney and Ureter; Ureteric Reflux; Congenital Ureteric Anomaly; Benign Renal Neoplasm
• Intervention / Treatment: Drug: spinal analgesia with morphine and bupivacaine; Drug: lidocaine infusion

Detailed Description

Please refer to CTIS

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hans Bahlmann, MD PhD; Phone Number: +46739312281; Email: hans.bahlmann@regionostergotland.se
• Study Contact Backup: Name: Martin Holmberg, MD; Phone Number: +46101033932; Email: martin.holmberg@regionostergotland.se

Study Locations

• Sweden
  • Kalmar, Sweden
    • Recruiting
    • Länssjukhuset i Kalmar
    • Contact: Torgny Persson, MD; Phone Number: +46-10-3583353; Email: torgny.persson@regionkalmar.se
    • Contact: Anna Maria Stoor, RN; Email: annamaria.stoor@regionkalmar.se
  • Linköping, Sweden
    • Recruiting
    • University Hospital Linköping
    • Contact: Martin Holmberg, MD; Phone Number: +46101033932; Email: martin.holmberg@regionostergotland.se
  • Vaxjo, Sweden
    • Not yet recruiting
    • Centrallasarettet Växjö
    • Contact: Marianna Vizbor, MD; Phone Number: +46 470 58 9182; Email: marianna.vizbor@kronoberg.se
    • Contact: Elin Alfson, RN; Email: elin.alfson@kronoberg.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient is scheduled for elective robotic-assisted upper urinary tract surgery at one of the participating hospitals
• The patient gives oral and written informed consent after having received oral and writen information about the study

Exclusion Criteria:

• The patient has a ASA-class of IV or above
• The patient is a minor or declared incompetent, has severe psychiatric disease or is expected not to be able to understand the study information due to severe restrictions in vision, hearing, cognition, reading or Swedish language abilities
• The patient is a female who is pregnant or breastfeeding
• The patient is a pre-menopausal female who has not undergone sterilisation, hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy, and is not using highly-effective contraception with low user-dependency and cannot provide a negative pregnancy test
• The patient is scheduled for emergency surgery
• Research staff not available
• Scheduled significant simultaneous surgery on another organ
• The anesthesiologist in charge has planned spinal or epidural analgesia
• The patient has clear contraindications to spinal analgesia, e.g. severe coagulopathy, severe aortic stenosis, previous back surgery with rods, or spinal analgesia can be expected to be technically challenging (severe obesity, severe scoliosis)
• The patient has clear contraindications to lidocaine infusion, e.g. proven allergy to local anesthetics, myasthenia gravis, renail failure (eGFR < 30), hepatic failure caused by acute hepatitis or cirrhosis (Child-Pugh B or higher, severe cardiac arrythmias or insuffiency (NYHA IIIb or higher)
• The patient has previously participated in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: spinal analgesia; single shot spinal analgesia with 0.2-0.3 mg morphine and 10-20 mg bupivacaine before surgery	Drug: spinal analgesia with morphine and bupivacaine; single shot spinal analgesia with 0.2-0.3 mg morphine and 10-20 mg bupivacaine before surgery; Other Names: morphine spinal
Active Comparator: lidocaine infusion; intraoperative intravenous infusion of lidocaine at a rate of 2 mg/kg/t (Ideal Body Weight)	Drug: lidocaine infusion; intraoperative intravenous infusion of lidocaine at a rate of 2 mg/kg/t after a bolus of 2 mg/kg (Ideal Body Weight if BMI > 22, otherwise ABW); Other Names: xylocaine iv

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QoR-15 score at postoperative day 1	Quality of Recovery-15 score ranges from 0 to 150 with 0 reflecting zero wellbeing and 150 reflecting perfect wellbeing. The primary research hypothesis is that the reduction in QoR-15 from baseline before surgery to the first postoperative day (POD 1) is at least 8.0 points less in the morphine spinal group compared to the control group treated with intravenous lidocaine.	First day after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QoR-15 score preoperatively	Quality of Recovery-15 score ranges from 0 to 150 with 0 reflecting zero wellbeing and 150 reflecting perfect wellbeing.	Any time between inclusion and the night before surgery
QoR-15 score at postoperative day 7	Quality of Recovery-15 score ranges from 0 to 150 with 0 reflecting zero wellbeing and 150 reflecting perfect wellbeing.	Seventh day after surgery
Pain (NRS) on POD 1-3	Numeric Rating Scale ranges from 0 to 10 with 0 reflecting absence of pain and 10 reflecting extreme pain.	First, second and third day after surgery
Pain (NRS) in rest and during motion at POD 7	Numeric Rating Scale ranges from 0 to 10 with 0 reflecting absence of pain and 10 reflecting extreme pain.	Seventh day after surgery
Amount of remifentanil in patients given remifentanil	Amount of remifentanil during anesthesia in patients given remifentanil expressed in mcg/kg/min as recorded on the anesthetic chart.	Intraoperatively
Amount of intraoperative opioids in patients not receiving remifentanil	Amount of intraoperative opioids in patients not receiving remifentanil expressed in mcg/kg/min morphine equivalents as recorded on the anesthetic chart.	Intraoperatively
Length of stay	Length of stay in calendary days	From first until thirtieth day after surgery
DAOH30	Days Alive and Out of Hospital defined as the number of full calendary days where the patient is not admitted to a hospital and not deceased	From first until thirtieth day after surgery
Requirement for opioids after discharge	Y/N, based on a telephone interview	From first until seventh day after surgery
Intraoperative fluid balance	Intraoperative fluid balance as recorded on the CRF in ml, defined by the estimated sum of administered fluids minus estimated bleeding, diuresis and other measurable losses.	Intraoperatively
Intraoperative Cardiac Index	Cardiac output corrected for Body Surface Area expressed in L/min/m2	Intraoperative
Intraoperative Stroke Volume Index	Stroke volume corrected for Body Surface Area expressed in mL/m2	Intraoperative
Intraoperative Cardiac Power Index	Cardiac Power Output corrected för Body Surface Area, expressed in Watt/m2, with higher values implying better cardiac performance.	Intraoperative
Intraoperative dPmx	Maximum increase in arterial pressure during a cardiac cycle, expressed in mmHg/second, with higher values implying better cardiac contractility.	Intraoperative
Intraoperative Pulse Pressure Variation	Determined as the ratio of the difference between the maximal and minimal values of pulse pressure over the mean of these two values and expressed as a percentage	Intraoperative
Intraoperative Stroke Volume Variation	Determined as the ratio of the difference between the maximal and minimal values of stroke volume over the mean of these two values and expressed as a percentage	Intraoperative
Intraoperative Systemic Vascular Resistance Index	Intraoperative Systemic Vascular Resistance corrected for Body Surface Area	Intraoperative
Biochemical markers of inflammation	To be specified later during the study (samples are stored for later analysis)	Day of surgery and first and third day after surgery.
Intraoperative dynamic arterial elastance	Determined as Pulse Pressure Variation divided by Stroke Volume Variation	Intraoperative
Pain (NRS) in rest and during motion 2hrs after arrival to the PACU/ICU/HDU	Numeric Rating Scale ranges from 0 to 10 with 0 reflecting absence of pain and 10 reflecting extreme pain.	2 hrs after arrival to the PACU
Time from arrival in the OR to start of surgery	Time from entering the OR to first incision or start of endoscopy, whichever comes first, up to 4 hrs.	Time from entering the OR to first incision or start of endoscopy, whichever comes first, up to 4 hrs.
Time from end of surgery until leaving the OR	Time from end of surgery (removing of surgical drapes or finishing of endoscopy, whichever comes last) until leaving the OR, up to 4 hrs	Time from end of surgery (removing of surgical drapes or finishing of endoscopy, whichever comes last) until leaving the OR, up to 4 hrs
Incidence of unplanned termination of the lidocaine infusion	Incidence of unplanned termination of the lidocaine infusion	Intraoperatively
Length of stay at the PACU/ICU/HDU	Length of stay at the PACU/ICU/HDU (from first to final recording of any vital sign by the electronic patient data management system), up to 30 days	Length of stay at the PACU (from first to final recording of any vital sign by the electronic patient data management system), up to 30 days
Amount of opioids administred at the PACU/ICU/HDU during the first 24 hrs after end of surgery	Amount of opioids administered at the PACU/ICU/HDU expressed in mcg/kg morphine equivalents as recorded on the post-anesthetic chart.	During stay at the PACU (from first to final recording of any vital sign by the electronic patient data management system), up to 30 days
PONV requiring treatment at 0-6 hours and 6-24 hours postoperatively as well as during the whole postoperative stay	PONV requiring treatment at 0-6 hours and 6-24 hours	At 0-6 hours and 6-24 hours postoperatively as well as during the whole postoperative stay
"Time out-of-bed" on POD 1-3	"Time out-of-bed" on POD 1-3	First, second and third day after surgery
Amount of opioids administered during the first 24 hours at the PACU/ICU/HD and on the ward	Amount of opioids expressed in mcg/kg morphine equivalents administered during the first 24 hours at the PACU/ICU/HD and on the ward as recorded on the ward chart.	During the first 24 hours at the PACU and on the ward
First POD passing gases	First POD passing gases	From first until seventh day after surgery
First POD passing stool	First POD passing stool	From first until seventh day after surgery
Incidence of pruritus	Incidence of pruritus	From first until seventh day after surgery
Postoperative complications untill POD 30	Postoperative complications untill POD 30	From first until thirtieth day after surgery
Incidence of respiratory depression leading to the use of a mu-antagonist within 48 hours of induction of anesthesia	Incidence of respiratory depression leading to the use of a mu-antagonist within 48 hours	From induction of anesthesia until 48 hours after induction of anesthesia
Time with low blood pressure during anesthesia	Time with low blood pressure during anesthesia	Intraoperatively
Lowest MAP within 10 minutes after induction of anesthesia	Lowest MAP within 10 minutes after induction of anesthesia	Within 10 minutes after induction of anesthesia
Highest MAP within 10 minutes of start of abdominal insufflation	Highest MAP within 10 minutes of start of abdominal insufflation	Within 10 minutes of abdominal insufflation
Fraction of patients needing norepinephrine within 15 minutes after start of abdominal insufflation	Fraction of patients needing norepinephrine within 15 minutes after start of abdominal insufflation	From anesthesia induction until 15 minutes after start of abdominal insufflation
Fraction of patients needing norepinephrine intraoperatively (later than 15 minutes after start of abdominal insufflation)	Fraction of patients needing norepinephrine intraoperatively (later than 15 minutes after start of abdominal insufflation)	Intraoperatively (later than 15 minutes after start of abdominal insufflation)
Average infusion rate of norepinephrine, in patients receiving norepinephrine, before 15 minutes after start of abdominal insufflation	Average infusion rate of norepinephrine, in patients receiving norepinephrine, before 15 minutes after start of abdominal insufflation	From anesthesia induction until 15 minutes after start of abdominal insufflation until end of anesthesiaon, up to 48 hours
Average infusion rate of norepinephrine, in patients receiving norepinephrine, after 15 minutes after start of abdominal insufflation	Average infusion rate of norepinephrine, in patients receiving norepinephrine, after 15 minutes after start of abdominal insufflation	From 15 minutes after start of abdominal insufflation until end of anesthesia (extubation), up to 48 hrs
Intraoperative heart rate	Intraoperative heart rate	Intraoperative

Collaborators and Investigators

• Sponsor: Hans Bahlmann
• Collaborators: Linkoeping University
• Investigators: Principal Investigator: Martin Holmberg, University Hospital, Linkoeping

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 24, 2024
• First Submitted That Met QC Criteria: March 29, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urolithiasis; Urologic Neoplasms; Ureteral Diseases; Urinary Bladder Diseases; Nephrolithiasis; Ureteral Neoplasms; Kidney Neoplasms; Vesico-Ureteral Reflux; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Bupivacaine; Morphine
• Other Study ID Numbers: 2023-505941-21-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be made available on reasonable request
• IPD Sharing Time Frame: Within 2 months of publication of the data involved
• IPD Sharing Access Criteria: reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No