Oxidative StressPhase 4NCT07903259
Effect of Paracetamol Administration Timing on Oxidative Stress in Children Undergoing Sevoflurane Anesthesia
A Phase 4 study testing paracetamol (acetaminophen) solution commercial in people with Oxidative Stress and Sevoflurane Anaesthesia, run by University of Belgrade at 1 site in Serbia.
Trial summary
This study investigated the effects of paracetamol administration on oxidative stress in children undergoing inguinal hernia surgery under sevoflurane-based general anesthesia. Oxidative stress occurs when the production of potentially harmful molecules exceeds the body's antioxidant defenses. Read more about this study
- Who is it for?
- Ages 2 months to 18 years
- Conditions the study is for
- Oxidative Stress, Sevoflurane Anaesthesia
- What is being tested?
- paracetamol (acetaminophen) solution commercial
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteSerbia
- Study dates
- 29 Jul 2019to 25 Apr 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Pediatric patients classified as American Society of Anesthesiologists (ASA) Physical Status I scheduled for elective inguinal hernia surgery.
Who cannot join
- Known allergy or hypersensitivity to any of the medications used in the study protocol.
- Previous use of multivitamin preparations or dietary supplements.
Trial locations and contacts
1 site in 1 country.
Serbia1 site
Institute for Mother and Child Health Care of Serbia "Dr Vukan Čupić"
Belgrade
About this study
Official title: Effect of Paracetamol on Oxidative Stress Parameters in Pediatric Patients Undergoing Inguinal Hernia Surgery During Sevoflurane-Based Anesthesia
This study investigated the effects of paracetamol administration on oxidative stress in children undergoing inguinal hernia surgery under sevoflurane-based general anesthesia.
Oxidative stress occurs when the production of potentially harmful molecules exceeds the body's antioxidant defenses. Anesthesia and surgery may influence this balance.
Read more
The study compared two groups of children who received intravenous paracetamol at different stages of anesthesia. In one group, paracetamol was administered before premedication with midazolam and induction of anesthesia with sevoflurane. In the other group, paracetamol was administered after midazolam premedication and induction of anesthesia.
Blood samples were collected at four predefined time points to measure markers of oxidative stress and antioxidant defense.
The aim was to determine whether the timing of paracetamol administration influenced oxidative stress parameters in children undergoing surgery.
Read the detailed description
This interventional study was conducted as part of a doctoral research project to investigate the effects of paracetamol administration timing on oxidative stress in pediatric patients undergoing inguinal hernia surgery under sevoflurane-based general anesthesia.
Background and Rationale
Oxidative stress results from an imbalance between the production of reactive oxygen species and the body's antioxidant defense mechanisms. General anesthesia and surgical procedures may affect oxidative balance. Paracetamol is widely used for perioperative analgesia and has been investigated for its potential effects on oxidative processes.
Study Procedures
The study included two groups of pediatric patients who received intravenous paracetamol at different stages of the anesthetic procedure.
In the first group (PS), paracetamol was administered before midazolam premedication and induction of anesthesia with sevoflurane.
In the second group (SP), midazolam premedication and induction of anesthesia with sevoflurane preceded paracetamol administration.
Anesthesia was induced with sevoflurane, followed by administration of the medications required for airway management and maintenance of general anesthesia.
Blood samples were collected at four predefined time points according to the study protocol.
Biochemical Assessment
Oxidative stress and antioxidant defense were assessed using the following biochemical parameters:
Erythrocyte antioxidant enzyme activities: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR).
Plasma parameters: malondialdehyde (MDA), sulfhydryl (SH) groups, total glutathione, superoxide dismutase (SOD), and nitric oxide metabolites (NOx).
Study Objective
The objective was to evaluate changes in oxidative stress parameters during the perioperative period and to determine whether the timing of paracetamol administration influenced these changes in children undergoing sevoflurane-based anesthesia.
- Conditions
- Oxidative Stress, Sevoflurane Anaesthesia
- Being tested
- paracetamol (acetaminophen) solution commercial
- Keywords
- paracetamol, sevoflurane, oxidative stress, pediatric anesthesia, Antioxidant Enzymes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
paracetamol (acetaminophen) solution commercialDrug
Intravenous paracetamol (10 mg/mL formulation) was administered over 15 minutes. In the PS group, paracetamol was administered before midazolam premedication and induction of anesthesia with sevoflurane.
In the SP group, paracetamol was administered after midazolam premedication and induction of anesthesia with sevoflurane.
Both groups underwent sevoflurane-based general anesthesia according to the same anesthetic protocol. The intervention under investigation was the timing of paracetamol administration in relation to premedication and anesthetic induction.
| Study group | Role | What they receive |
|---|---|---|
| PS - Paracetamol Before Sevoflurane | Experimental | Participants received intravenous paracetamol before midazolam premedication and induction of general anesthesia with sevoflurane. Oxidative stress parameters were assessed at four predefined sampling time points. Receives: Drug: paracetamol (acetaminophen) solution commercial |
| SP - Paracetamol After Sevoflurane Induction | Experimental | Participants received intravenous paracetamol after midazolam premedication and induction of general anesthesia with sevoflurane. Oxidative stress parameters were assessed at four predefined sampling time points. Receives: Drug: paracetamol (acetaminophen) solution commercial |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Erythrocyte Superoxide Dismutase (SOD) Activity
Erythrocyte superoxide dismutase (SOD) activity was measured spectrophotometrically and expressed in U/g Hb. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision
Change in Erythrocyte Catalase (CAT) Activity
Erythrocyte catalase (CAT) activity was measured spectrophotometrically as an indicator of antioxidant defense. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Change in Erythrocyte Glutathione Peroxidase (GPx) Activity
Erythrocyte glutathione peroxidase (GPx) activity was measured spectrophotometrically as an indicator of enzymatic antioxidant defense. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Change in Erythrocyte Glutathione Reductase (GR) Activity
Erythrocyte glutathione reductase (GR) activity was measured spectrophotometrically as an indicator of enzymatic antioxidant defense. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Change in Plasma Malondialdehyde (MDA) Concentration
Plasma malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation and oxidative stress. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Change in Plasma Total Sulfhydryl (SH) Group Levels
Plasma total sulfhydryl (SH) group levels were measured using a spectrophotometric method based on 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) as an indicator of plasma antioxidant status. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Change in Plasma Total Glutathione Concentration
Plasma total glutathione concentration was measured as an indicator of antioxidant defense and redox homeostasis. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Change in Plasma Superoxide Dismutase (SOD) Activity
Plasma superoxide dismutase (SOD) activity was measured as an indicator of extracellular antioxidant defense. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Change in Plasma Nitric Oxide Metabolite (NOx) Concentration
Plasma nitric oxide metabolites (NOx), comprising nitrite and nitrate, were measured using the Griess reaction following nitrate reduction. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Measured: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2026
- Study start29 Jul 2019
- Primary completion25 Apr 2023
- Study completion25 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oxidative StressStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants were assigned to two parallel groups according to the timing of intravenous paracetamol administration. In the PS group, paracetamol was administered before midazolam premedication and sevoflurane induction. In the SP group, paracetamol was administered after midazolam premedication and sevoflurane induction. Each participant received only one intervention sequence.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Belgrade
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sladjana Vasiljevic, University of Belgrade
- Investigators
- Sladjana M Vasiljevic, MD, Principal investigator, Medical Faculty, University of Belgrade
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07903259
- Sponsor's protocol ID
- PARA-OXSTRESS-01
- Status last verified
- Oct 2026
- First submitted
- 21 Oct 2026
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared because the study involved pediatric patients and data sharing was not included in the original study protocol or informed consent process. Study results will be reported in aggregate form to protect participant confidentiality.
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Paracetamol on Oxidative Stress Parameters in Pediatric Patients Undergoing Inguinal Hernia Surgery During Sevoflurane-Based Anesthesia
- ClinicalTrials.gov ID
- NCT07903259
- Acronym / sponsor ID
- PARA-OXSTRESS-01
- Conditions
- Oxidative Stress, Sevoflurane Anaesthesia
- Keywords
- paracetamol, sevoflurane, oxidative stress, pediatric anesthesia, Antioxidant Enzymes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of BelgradeUniversity, hospital or other
- Study start
- 29 Jul 2019 (actual)
- Primary completion
- 25 Apr 2023 (actual)
- Study completion
- 25 Apr 2023 (actual)
- First posted
- 29 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study investigated the effects of paracetamol administration on oxidative stress in children undergoing inguinal hernia surgery under sevoflurane-based general anesthesia.
Oxidative stress occurs when the production of potentially harmful molecules exceeds the body's antioxidant defenses. Anesthesia and surgery may influence this balance.
The study compared two groups of children who received intravenous paracetamol at different stages of anesthesia. In one group, paracetamol was administered before premedication with midazolam and induction of anesthesia with sevoflurane. In the other group, paracetamol was administered after midazolam premedication and induction of anesthesia.
Blood samples were collected at four predefined time points to measure markers of oxidative stress and antioxidant defense.
The aim was to determine whether the timing of paracetamol administration influenced oxidative stress parameters in children undergoing surgery.
Detailed description
This interventional study was conducted as part of a doctoral research project to investigate the effects of paracetamol administration timing on oxidative stress in pediatric patients undergoing inguinal hernia surgery under sevoflurane-based general anesthesia.
Background and Rationale
Oxidative stress results from an imbalance between the production of reactive oxygen species and the body's antioxidant defense mechanisms. General anesthesia and surgical procedures may affect oxidative balance. Paracetamol is widely used for perioperative analgesia and has been investigated for its potential effects on oxidative processes.
Study Procedures
The study included two groups of pediatric patients who received intravenous paracetamol at different stages of the anesthetic procedure.
In the first group (PS), paracetamol was administered before midazolam premedication and induction of anesthesia with sevoflurane.
In the second group (SP), midazolam premedication and induction of anesthesia with sevoflurane preceded paracetamol administration.
Anesthesia was induced with sevoflurane, followed by administration of the medications required for airway management and maintenance of general anesthesia.
Blood samples were collected at four predefined time points according to the study protocol.
Biochemical Assessment
Oxidative stress and antioxidant defense were assessed using the following biochemical parameters:
Erythrocyte antioxidant enzyme activities: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR).
Plasma parameters: malondialdehyde (MDA), sulfhydryl (SH) groups, total glutathione, superoxide dismutase (SOD), and nitric oxide metabolites (NOx).
Study Objective
The objective was to evaluate changes in oxidative stress parameters during the perioperative period and to determine whether the timing of paracetamol administration influenced these changes in children undergoing sevoflurane-based anesthesia.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Participants were assigned to two parallel groups according to the timing of intravenous paracetamol administration. In the PS group, paracetamol was administered before midazolam premedication and sevoflurane induction. In the SP group, paracetamol was administered after midazolam premedication and sevoflurane induction. Each participant received only one intervention sequence.
| Arm | Type | Receives |
|---|---|---|
| PS - Paracetamol Before Sevoflurane | Experimental | Drug: paracetamol (acetaminophen) solution commercialParticipants received intravenous paracetamol before midazolam premedication and induction of general anesthesia with sevoflurane. Oxidative stress parameters were assessed at four predefined sampling time points. |
| SP - Paracetamol After Sevoflurane Induction | Experimental | Drug: paracetamol (acetaminophen) solution commercialParticipants received intravenous paracetamol after midazolam premedication and induction of general anesthesia with sevoflurane. Oxidative stress parameters were assessed at four predefined sampling time points. |
Who may qualify
- Ages
- 2 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Pediatric patients classified as American Society of Anesthesiologists (ASA) Physical Status I scheduled for elective inguinal hernia surgery.
Key exclusion criteria (2 listed)
- Known allergy or hypersensitivity to any of the medications used in the study protocol.
- Previous use of multivitamin preparations or dietary supplements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| paracetamol (acetaminophen) solution commercialIntravenous paracetamol (10 mg/mL formulation) was administered over 15 minutes. In the PS group, paracetamol was administered before midazolam premedication and induction of anesthesia with sevoflurane. In the SP group, paracetamol was administered after midazolam premedication and induction of anesthesia with sevoflurane. Both groups underwent sevoflurane-based general anesthesia according to the same anesthetic protocol. The intervention under investigation was the timing of paracetamol administration in relation to premedication and anesthetic induction. | Drug | PS - Paracetamol Before Sevoflurane, SP - Paracetamol After Sevoflurane Induction |
Primary outcome
Change in Erythrocyte Superoxide Dismutase (SOD) Activity
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision
Erythrocyte superoxide dismutase (SOD) activity was measured spectrophotometrically and expressed in U/g Hb. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Change in Erythrocyte Catalase (CAT) Activity
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Erythrocyte catalase (CAT) activity was measured spectrophotometrically as an indicator of antioxidant defense. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Change in Erythrocyte Glutathione Peroxidase (GPx) Activity
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Erythrocyte glutathione peroxidase (GPx) activity was measured spectrophotometrically as an indicator of enzymatic antioxidant defense. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Change in Erythrocyte Glutathione Reductase (GR) Activity
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Erythrocyte glutathione reductase (GR) activity was measured spectrophotometrically as an indicator of enzymatic antioxidant defense. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Change in Plasma Malondialdehyde (MDA) Concentration
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Plasma malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation and oxidative stress. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Change in Plasma Total Sulfhydryl (SH) Group Levels
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Plasma total sulfhydryl (SH) group levels were measured using a spectrophotometric method based on 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) as an indicator of plasma antioxidant status. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Change in Plasma Total Glutathione Concentration
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Plasma total glutathione concentration was measured as an indicator of antioxidant defense and redox homeostasis. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Change in Plasma Superoxide Dismutase (SOD) Activity
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Plasma superoxide dismutase (SOD) activity was measured as an indicator of extracellular antioxidant defense. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Change in Plasma Nitric Oxide Metabolite (NOx) Concentration
Time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision.
Plasma nitric oxide metabolites (NOx), comprising nitrite and nitrate, were measured using the Griess reaction following nitrate reduction. Changes across four predefined blood sampling points were evaluated and compared between the two paracetamol administration groups.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared because the study involved pediatric patients and data sharing was not included in the original study protocol or informed consent process. Study results will be reported in aggregate form to protect participant confidentiality.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sladjana M Vasiljevic, MD principal investigator
Medical Faculty, University of Belgrade
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing paracetamol (acetaminophen) solution commercial in people with Oxidative Stress and Sevoflurane Anaesthesia, run by University of Belgrade at 1 site in Serbia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Erythrocyte Superoxide Dismutase (SOD) Activity (time frame: Four perioperative sampling points, from baseline to the final blood sample before surgical incision). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.