Testing whether ketamine and magnesium sulfate can reduce pain after kidney removal surgery

ISRCTN	ISRCTN83633282
DOI	https://doi.org/10.1186/ISRCTN83633282
Sponsor	University clinical center of Republika Srpska
Funder	University Clinical Center of Serbia

Submission date: 12/03/2026
Registration date: 14/03/2026
Last edited: 05/05/2026

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Nebojsa Ladjevic
Scientific, Principal investigator, Public

Faculty of Medicine, University of Belgrade, Dr Subotica 8 St.
Belgrade
11000
Serbia

ORCID ID	0000-0001-9569-4954
Phone	+38111 3636300
Email	nebojsa.ladjevic@med.bg.ac.rs

Prof Zoran Dzamic
Public, Scientific

Faculty of Medicine, University of Belgrade, Dr Subotica 8 St.
Belgrade
11000
Serbia

ORCID ID	0009-0001-8953-2294
Phone	+38111 3636300
Email	dzamiczoran960@gmail.com

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Blinded (masking used)
Control	Placebo
Assignment	Factorial
Purpose	Treatment
Scientific title	Sequence-dependent analgesic efficacy of perioperative intravenous ketamine and magnesium sulfate in patients undergoing open radical nephrectomy: a randomized, double-blind, placebo-controlled clinical trial
Study objectives	To evaluate the sequence-dependent analgesic efficacy of perioperative intravenous ketamine and magnesium sulfate in patients undergoing elective open radical nephrectomy, and to determine whether the order of administration influences postoperative pain intensity and opioid consumption.
Ethics approval(s)	Approved 13/07/2017, Institutional Ethics Committee of the University Clinical Centre of Serbia (Pasterova 2, Belgrade, 11000, Serbia; +381 11 366 2100; eticki.odbor.ukcs@gmail.com), ref: 361/15
Health condition(s) or problem(s) studied	Postoperative pain, renal cell carcinoma, radical nephrectomy, multimodal analgesia
Intervention	Patients were randomized into one of nine subgroups defined by two sequential intravenous bolus injections (Drug A administered immediately after induction of anesthesia, Drug B administered 10 minutes later): Ketamine 0.2 mg/kg, MgSO4 15 mg/kg, or placebo (0.9% NaCl) in all possible combinations. All solutions were visually indistinguishable and administered in identical syringes. There was no postoperative continuation of the study drugs. The total duration of active treatment was therefore approximately 10–20 minutes per participant. Postoperative follow-up was conducted for 48 hours, with pain and safety assessments at 14 standardised time points (0, 30 min, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, and 48 hours post-surgery). Randomisation was performed prior to study commencement using a computer-based random number generator with block randomisation. The randomisation sequence was maintained by a designated independent coordinator. All study solutions were prepared by an anaesthesia nurse not involved in patient care, in identical syringes of equal volume, ensuring allocation concealment.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Ketamine; magnesium sulfate (mgso4); placebo (0.9% nacl)
Primary outcome measure(s)	Postoperative pain intensity at rest and on movement measured using Numerical Rating Scale (NRS, 0-10) at 0, 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, and 48 hours after PACU/ICU admission
Key secondary outcome measure(s)
Completion date	15/02/2026

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	80 Years
Sex	All
Target sample size at registration	208
Total final enrolment	208
Key inclusion criteria	1. Age ≥18 years 2. ASA physical status class I–III 3. Unilateral renal tumor scheduled for elective open radical nephrectomy
Key exclusion criteria	1. Resting bradycardia or AV block 2. NYHA functional class greater than 2 3. GFR less than 50 ml/min 4. Severe COPD or asthma 5. Poorly controlled arterial hypertension 6. Severe hepatic impairment 7. Elevated IOP or ICP 8. Significant psychiatric comorbidity 9. Known allergy to study medications 10. Pre-existing chronic pain syndrome 11. Regular analgesic use in the month preceding surgery
Date of first enrolment	01/08/2017
Date of final enrolment	31/01/2026

Locations

Countries of recruitment

Serbia

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		15/04/2026	05/05/2026	Yes	No
Protocol file			13/03/2026	No	No

Additional files

49194 Study Protocol.pdf: Protocol file

Editorial Notes

05/05/2026: Publication reference added.
13/03/2026: Trial's existence confirmed by Institutional Ethics Committee of the University Clinical Centre of Serbia.