Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 2:53 AM
Ignite Modification Date:
2025-12-25 @ 2:53 AM
NCT ID:
NCT07144033
Brief Summary:
This study is a single-center, phase II, randomized, placebo-controlled, Bayesian-designed, double-blinded trial
Goal and Questions:
The primary goal is to evaluate if a combination of taurine and butyrate can reduce chronic postsurgical pain (CPSP) in adult cardiac surgical patients. The study also aims to determine if these compounds are safe, effective in perioperative pain control, and feasible for improving postoperative outcomes.
Participants:
The study will include adult patients (aged 18 or older) undergoing elective coronary artery bypass graft (CABG), valve repair/replacement, combined CABG/valve, or major aortic procedure via sternotomy. Exclusion criteria include emergency surgery, redo surgery, a history of chronic pain or chronic opioid/sedative use, and an estimated glomerular filtration rate (eGFR) less than 30 mL/min. The target sample size is 216 patients.
Intervention group: Patients will receive 4g of taurine and 4.8g of sodium butyrate orally once daily, starting the day before surgery and continuing for three months post-surgery.
Placebo group: Patients will receive indistinguishable placebo capsules orally once daily, following the same schedule as the intervention group.
Primary Outcome: The incidence of chronic postsurgical pain at 3 months,
Secondary Outcomes:
Quality of Recovery Questionnaire (QoR-15) at 72 hours after extubation.
Pain scores (NRS) at rest and with movement at 12, 24, 48, and 72 hours post-extubation.
Postoperative morphine requirements and time to first morphine rescue.
Incidence of opioid-related side effects, such as postoperative nausea and vomiting (PONV).
Duration of mechanical ventilation, and length of stay in the ICU and hospital.
Long-term pain assessment using the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), Brief Pain Inventory (BPI) Interference Scale, and Neuropathic Pain Questionnaire (NPQ) at 1, 3, 6, and 12 months post-surgery
Proteomic analysis:
Blood samples within 72 hours after surgery will be collected for proteomic analysis to investigate predictors for chronic postsurgical pain.
Detailed Description:
INTRODUCTION
Managing pain after cardiac surgery is a complex challenge. Traditional pain medications like opioids and NSAIDs are effective but come with significant side effects, including addiction, respiratory issues, and organ damage. This has led researchers to look for safer alternatives. Two promising compounds are butyrate and taurine. Butyrate is a short-chain fatty acid produced by gut bacteria. It helps reduce inflammation and pain by influencing both the central and peripheral nervous systems. Studies show that it can alleviate various types of pain, from visceral to neuropathic, and may help prevent chronic pain after surgery. Taurine is an amino acid that modulates neurotransmitters and ion channels in the nervous system, providing an analgesic effect. It may also reduce opioid tolerance, which is crucial for managing long-term pain. The innovative approach of this research is to use both butyrate and taurine together. Butyrate's anti-inflammatory properties complement taurine's pain-modulating effects, creating a synergistic combination. This could not only reduce the need for traditional opioids-thus minimizing their side effects-but also improve the overall quality of recovery for cardiac surgery patients. Both compounds are safe, cost-effective, and readily available as oral supplements, making them a practical and viable alternative for modern pain management.
METHODS AND ANALYSIS
Study population and design This is a single-centre, phase II, randomized, placebo-controlled, Bayesian designed double-blinded trial conducted at Prince of Wales Hospital, a tertiary hospital in Hong Kong.
Randomization and Concealment Patients are randomly allocated to combined taurine/butyrate or identical-looking capsules by drawing sequentially numbered, coded, sealed, opaque envelops, each containing the type of intervention assignment or placebo. The sealed envelopes for randomization are prepared by a third party who took no further part in the study. The study investigators, the primary care team and the participants are masked to the group assignments. This is achieved by using an indistinguishable placebo (a proprietary product from Colorcon called StarCap - a mixture of Pregelatinized Maize Starch and Maize Starch) capsules manufactured by an independent pharmaceutical company in Western Australia.
Blood sampling Animal models suggested a positive correlation of serum butyrate concentration on T-cell function for treatment responsive cancer patients in the range of 0.1-0.2 mcg/ml, and an inverse relationship of a similar serum concentration in treatment response in schizophrenic patients. However, the plasma level that is required for analgesia in humans has not yet been established. To ensure the study drugs reach a clinically meaningful plasma concentration after gut absorption and hepatic first-pass, blood samples will be collected within 72-hour after surgery to analyse taurine and butyrate levels.
Since postoperative inflammation peaks at 12-24 hours and declines to normal at 48-72 hours in the absence of complications, blood samples within 72-hour after surgery will be collected for proteomic analysis. By integrating proteomic data with perioperative clinical variables, predictors for chronic postsurgical pain, as well as modifiable factors that influence pain outcomes can be identified.
Compliance check Drug compliance will be check via blood sampling and rectal swab. Plasma levels of taurine and butyrate will be measured at baseline after taking informed consent, and at 1 and 3 months after surgery. Similarly, rectal swab for butyrate and taurine level will be measured at the same time points. Rectal swab is performed by the research nurse. Since the study drug capsules will all be given to the participants before post-surgical hospital discharge, the number of remaining capsules will be counted during follow-up visits to check for the compliance.
Statistical Analysis The study adopts a Bayesian framework to evaluate the efficacy of a novel combination of butyrate and taurine in reducing the incidence of CPSP at 3 months. A sample size of 180 patients (90 per arm) based on Bayesian simulation (Department of Biostatistics, The University of Texas MD Anderson Cancer Centre, https://biostatistics.mdanderson.org/shinyapps/rBOP2/) indicates a power 87.0% to detect an absolute risk reduction in chronic pain incidence of 20% (from a baseline of 30% to 10%). The clinically meaningful absolute risk reduction in CPSP is set at 6%. Should non-futility be demonstrated in this phase II trial, it will provide baseline data to inform future research for demonstration on superiority.
Considering a drop-out of 20%, the overall sample size is increased to 216 patients (108 per arm). Blinded interim analyses will be conducted at every 72 randomized patients until the target sample size 216 are randomized. The conditions for stopping for superiority and futility are as follows:
* Stopping for Efficacy: If the posterior probability of a clinically meaningful reduction in CPSP (≥6%) exceeds 95%, the trial will stop, and the combination of butyrate and taurine will be deemed effective.
* Stopping for futility: If the posterior probability of achieving a meaningful reduction in CPSP incidence is less than 5%, the trial will stop and the intervention will be considered ineffective. A demonstrated non-futility can provide baseline data to inform future larger-scale trials with adequate power to demonstrate superiority.
* Continuing to the next stage: If the posterior probability lies between 5% and 95%, the trial will proceed to the next interim analysis, and an additional 66 patients (33 per group) will be recruited.
Analysis of Posterior Probabilities
At each stage, the posterior probability of achieving a ≥6% reduction in CPSP incidence will be calculated using the Bayesian hierarchical model as described above. The posterior distribution of the effect size will be summarized by:
* The posterior mean and 95% credible intervals for the reduction in CPSP incidence
* The posterior probability of achieving the predicted minimum clinically important difference (MCID) of 6%.
Continuous outcomes will be analyzed using Bayesian hierarchical models and reported as mean (standard deviation) or median (interquartile range) as appropriate after checking for normality using the Shapiro-Wilk's test. Categorical outcomes will be compared with Chi-square test. Generalized Estimating Equations (GEE) models will be conducted to evaluate the analgesia time effects between group. SPSS 27.0 (IBM Corp, Armonk, NY) is used for data analyses and Stata V.14 (Stata, College Station, Texas, USA) is used to conduct GEE with a Gaussian distribution, identity-link function, exchangeable correlation with robust standard error (SE). Level of significance will be set at P\<0.05 without adjusting for multiple comparisons.
Study:
NCT07144033
Study Brief:
Protocol Section:
NCT07144033