NCT07528612

MAG-PAIN - MAGnesium for Postoperative Analgesia In the Newly Delivered

Effect of Intravenous Magnesiumsulfate on Postoperative Pain in Patients Undergoing Cesarean Section: The Magnesium for Postoperative Analgesia In the Newly Delivered, The MAG-PAIN Randomized Controlled Trial.

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: Region Halland · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study aims to investigate whether a commonly used medicine, magnesium, can help reduce pain after a Caesarean section. A total of 150 participants will be included. Their usual medical care will not change, and participation is entirely voluntary. The purpose of the study is to determine whether magnesium can improve pain relief after surgery and support faster recovery and bonding with the newborn. Before the operation, potential participants will receive a text message containing a short questionnaire about their background and their expectations regarding postoperative pain. On the day of surgery, all patients will receive two intravenous lines as part of routine care. Those who participate in the study will be asked to rate how painful this insertion was on a scale from one to ten. The participants will then be randomly assigned to receive either magnesium or a saltwater solution through a 100 ml drip, which is administered after the baby is born. Neither participants nor the clinical staff will know which solution has been given, and no blood samples will be collected. After the procedure, participants will be asked several times about their pain level. During the first three days after the operation, each participant will receive one text message per day with a short questionnaire about their pain, general recovery, and early bonding with their newborn. Fourteen days after the operation, and again three months later, they will receive additional questionnaires similar to the earlier ones. Each questionnaire takes approximately five to seven minutes to complete, and no extra hospital visits are required. Magnesium can cause side effects, but the risks associated with the dose used in the study are low. The most common side effect is a brief burning sensation at the infusion site, which is not harmful. Magnesium is widely used in medical care, including in pregnant patients, and the study team considers the treatment safe. Because the medication is administered after birth, it does not affect the baby and does not increase risks during breastfeeding. All collected information will be handled securely and confidentially. Data will be coded so that individual participants cannot be directly identified, and only the research team will have access to the key linking codes to individuals. Participants have the right to access their data, request corrections, ask for deletion of their information, or limit how their data is used. The study has been approved by the Swedish Ethical Review Authority, and results will be published in a scientific journal without identifying any participant. No financial compensation is provided, but participants are covered by the usual patient and medication insurance. To ensure that the study is conducted correctly, authorized monitors or authorities may compare study data with medical records. These individuals must sign confidentiality agreements. By giving consent to participate, individuals allow this review. All data will be stored according to legal archiving requirements. Participation in the study is completely voluntary. Individuals may withdraw at any time, and if they do, their collected data will be deleted. Their medical care before, during, and after the operation will not be affected by their decision to participate or withdraw.

Detailed description

Background: Caesarean section is one of the most common surgical procedures worldwide, and the number performed continues to rise. Even with improvements in surgery and modern perioperative care, managing pain after a Caesarean section remains a major challenge. Severe postoperative pain can slow a mother's recovery and make it harder to bond with her baby or begin breastfeeding. Good pain control is important not only for comfort but also to prevent complications such as delayed movement, blood clots, and breathing problems. Post-Caesarean pain has many possible causes, involving both tissue-related (nociceptive) and nerve-related (neuropathic) components, which means pain management often needs to be tailored to each individual. Magnesium has been used in obstetrics for many years because of its medical benefits. It is commonly given to prevent or treat eclamptic seizures and to protect premature babies from brain injury. It can also stabilise blood pressure in pregnancy-related hypertension. Although its exact pain-relieving mechanism is not fully understood, magnesium is believed to reduce pain by influencing calcium movement in cells and by blocking NMDA receptors, which play a role in pain signalling. Some studies suggest that magnesium may help reduce pain after surgery. However, there are currently no official recommendations for its use specifically during Caesarean sections. This study aims to determine whether giving magnesium intravenously during planned Caesarean sections can improve postoperative pain and recovery. The study also examines whether magnesium leads to reduced opioid use and lower rates of nausea and vomiting after surgery. The researchers hypothesise that magnesium will be superior to standard care for both the primary and secondary outcomes. Study design: The MAG-PAIN trial is a double-blinded, randomized controlled study, meaning that participants are randomly placed into one of two groups, and neither they nor the medical staff know which treatment they receive. Inklusion and exclusion criteria: To take part, participants must be over 18, able to understand Swedish, and scheduled for an elective Caesarean section under spinal anaesthesia. People with advanced kidney disease, planned general anaesthesia, preeclampsia already treated with magnesium, or myasthenia gravis cannot join. All participants must give written and verbal consent and are free to withdraw at any time. Methods: Participants are informed about the study during their preoperative consultation and, if they agree to join, they complete a baseline form about their health and medical history. Participants are also assessed by an anaesthesiologist one to three days before surgery as part of routine care. On the day of surgery, a midwife places an IV line and records details such as needle size and any pain from insertion. A trained anaesthesia nurse, who is not clinically involved, performs randomization and prepares the study medication, ensuring that all clinical staff remain blinded. All patients receive standardized spinal anaesthesia and routine medication before the operation. After the baby is delivered and the umbilical cord is cut, the intervention group receives a magnesium infusion (20 mmol magnesium sulphate heptahydrate in 100 ml saline over 30 minutes), while the control group receives only saline for the same duration. Even if surgical or anaesthetic methods need to change during the procedure, participants remain in the study and are analyzed according to their assigned group (so called intention-to-treat). Pain will be assessed frequently during the first six hours after surgery, then again through text-message questionnaires sent at 24, 48, and 72 hours. These questionnaires ask about pain intensity, pain interference with daily activities, self-efficacy (confidence in managing recovery), breastfeeding quality, infant-mother bonding, medication use, and overall recovery quality using a validated 15-item score (QoR-15). Follow-up questionnaires are also sent at two weeks to measure subacute pain and at three months to assess long-term (persistent) postoperative pain. Randomization uses sealed envelopes prepared in blocks of ten to ensure balanced allocation. Blinding is maintained by preparing all infusions in identical bags labelled only "MAG-PAIN." Unblinding is allowed only if medically necessary or in case of a serious adverse event. All participants receive the hospital's usual standard of care aside from the study infusions and follow-up questionnaires. Nurses are trained in pain assessment and postoperative monitoring to ensure consistent data collection. Outcomes include measures of pain, nausea, opioid use, recovery quality, breastfeeding experience, and bonding, as well as safety indicators such as breathing problems, low blood pressure, need for emergency treatment, and any problems during the infusion. Respiratory and hemodynamic complications are defined using clear criteria such as low oxygen levels, need for extra oxygen, low blood pressure, use of vasopressors, CPR, uterotonic medication, or excessive bleeding. Discomfort during infusion, such as stopping the infusion early, is also recorded as a safety outcome Power analysis: The researchers consider a difference of 1.5 points on the pain scale (NRS) between the two groups to be clinically meaningful. Previous data suggest that women undergoing Caesarean section often report an average pain score of about 6 out of 10 during the first day after surgery. Using this information, and setting the statistical power at 80% and the significance level at 5%, the study needs 63 participants in each group to reliably detect a 1.5-point difference. Because some participants may drop out (about 20% expected), the study aims to recruit 150 participants in total. Data handling: All participant information will be stored securely in Entermedic, a Swedish data-management platform designed for medical research. Each participant gets an electronic study chart, and anaesthesia-related data are entered manually by staff. All follow-up questionnaires at 24, 48, and 72 hours, as well as at 14 days and 3 months, are sent automatically to participants as text messages, with built-in reminders to ensure data are collected on time. Study administrators also check daily for missing information. Entermedic follows strict data-protection rules, including ISO 27001 standards and full compliance with GDPR and Swedish patient-data laws. All data stay on servers located in Sweden and are never outsourced. Statistical plan: To verify that the data are normally distributed a test of normality will be conducted. The outcomes related to pain, self efficacy, pain interference, nausea, quality of recovery, breast feeding and infant-mother attachment are considered continuous. The investigators will use parametric tests for continuous variables. As the primary comparison involves differences in NRS scores between two groups, hypothesis testing will be performed using a two-sided Independent Samples t-test. For binary outcomes, the categorical data will be analysed using either the Chi-square test or Fisher's exact test. Secondary outcomes regarding acute pain trajectories will be analysed using a linear mixed effects model to account for the repeated NRS measurements at 6, 12, 24, 48, and 72 hours. Regarding other pain related secondary outcomes, we will group outcomes into clinically coherent families, defined by postoperative timepoints: 24 h (Family A), 48 h (Family B), 72 h (Family C), 14 days (Family D), and 90 days (Family E). Within each family, the secondary outcomes will be hierarchically ordered according to clinical relevance. A gatekeeping procedure will be applied within each family: the first outcome will be tested at the conventional two-sided α = 0.05 using an independent T-test. Subsequent outcomes in the same family will be tested sequentially. If the first outcome in that family is significant at the standard α = 0.05 all the following outcomes will be tested to the same level of significance. If the preceding outcome was non-significant, the next outcome will be tested using a conditional Hochberg stepup adjustment using α 0.05/2 = 0.025, thereby controlling the familywise error rate within that family. If the first and second hierarchical outcomes are found negative, then the third outcome within that family will be tested to the level of significance of 0.05/3 = 0.017. If the third outcome is also nonsignificant the fourth will be tested to the significance level of 0.05/4 = 0.013. This combined gatekeeping and conditional Hochberg approach preserves clinical prioritisation while limiting inflation of type I error across multiple secondary endpoints. Exploratory outcomes will be presented with unadjusted p - values and confidence intervals. To evaluate whether VCP predicts the development of APOP at the predefined postoperative timepoints, a multivariable logistic regression model with APOP (NRS ≥ 4) as the dependent variable will be set up. VCP (VCP ≥ 2.0), age, and number of previous deliveries will be independent variables based on clinical relevance. Regression coefficients will be presented as odds ratios with 95% confidence intervals. As adverse events (safety outcomes), related to the intervention, are expected to occur infrequently, their analysis will be conducted using Fisher's exact test and Independent Samples t-test. Monitoring and ethics: The study will be regularly monitored to ensure accurate data collection, patient safety, and adherence to the protocol. An Independent Data Monitoring Committee will review the trial, check for protocol violations, and assess any adverse events. All findings will be documented according to standard ethical requirements. The study will follow established clinical-trial guidelines (CONSORT) and has received approval from the Swedish Ethics Review Authority. Participation is voluntary, and written informed consent must be provided. Participants may withdraw at any time. The researchers declare no conflicts of interest. The hospital's routine procedures will be used to manage and document any complications, and no additional after-care is planned beyond standard practice. The results will be published in peer-reviewed scientific journals and shared with healthcare professionals and the public. Authorship will follow international guidelines (ICMJE). De-identified data and the full protocol may be shared upon reasonable request to the study team.

Conditions

• Postoperative Pain
• Quality of Recovery (QoR-15)
• Pain Prediction
• Magnesium Sulfate
• Pain Interference
• Self-Efficacy

Interventions

Type	Name	Description
DRUG	Magnesium group	When the neonate is delivered, the umbilical cord has been cut and uterotonic drugs has been administered, patients in the intervention group will receive an infusion of 20 mmol magnesium sulphate heptahydrate in 100 ml 0.9 % natrium chloride infor 30 minutes.
DRUG	Placebo	When the neonate is delivered, the umbilical cord has been cut and uterotonic drugs has been administered, patients in the the control group will receive an infusion of 100 ml 0.9% natrium chloride in 30 minutes.

Timeline

• Start date: 2026-04-02
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2026-04-14
• Last updated: 2026-04-17