Butyrate and Taurine for Chronic Postsurgical Pain in Adult Cardiac Surgical Patients: Bayesian Optimized Double-blinded Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 216
- 试验地点
- 1
- 主要终点
- Chronic postsurgical pain at 3 months
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients aged 18 or older
- •elective surgery
- •coronary artery bypass graft (CABG), valve repair/replacement, combined CABG/valve procedure, or major aortic procedure via sternotomy
排除标准
- •emergency surgery
- •redo surgery
- •history of chronic pain or on chronic opioids/sedatives
- •already taking taurine or butyrate prior to enrolment
- •renal failure with estimated glomerular filtration rate <30mL/min (calculated by Cockcroft-Gault formula)
- •re-operation within 24 hours after surgery
- •intraoperative use of remifentanil
- •inability to provide informed consent.
结局指标
主要结局
Chronic postsurgical pain at 3 months
时间窗: At 3 months after surgery
Incidence of chronic postsurgical pain based on the IASP definition
Chronic postsurgical pain at 3 months
时间窗: At 3 months after surgery
Incidence of chronic postsurgical pain based on the IASP definition
次要结局
- Oral analgesic use(Within 72 hours after surgery)
- surgical site infection(Within 30 days after surgery)
- Length of stay in ICU(Within 1 week after surgery)
- chronic postsurgical pain at 1 month(At 1 month after surgery)
- chronic postsurgical pain at 6 month(At 6 months after surgery)
- chronic postsurgical pain at 12 month(At 12 months after surgery)
- Brief Pain Inventory (BPI) at 1 month(At 1 month after surgery)
- Brief Pain Inventory (BPI) at 3 month(At 3 month after surgery)
- Brief Pain Inventory (BPI) at 6 month(At 6 month after surgery)
- Brief Pain Inventory (BPI) at 12 month(At 12 month after surgery)
- Neuropathic Pain Questionnaire (NPQ) at 1 month(At 1 month after surgery)
- Neuropathic Pain Questionnaire (NPQ) at 3 month(At 3 month after surgery)
- Neuropathic Pain Questionnaire (NPQ) at 6 month(At 6 month after surgery)
- Neuropathic Pain Questionnaire (NPQ) at 12 month(At 12 month after surgery)
- Proteomics analysis(Within 72 hours after surgery)
- Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) at 1 month(At 1 month after surgery)
- Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) at 3 month(At 3 month after surgery)
- Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) at 6 month(At 6 month after surgery)
- Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) at 12 month(At 12 month after surgery)
- Quality of Recovery Questionnaire (QoR-15)(At 72 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at rest at 12h(At 12 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at rest at 24h(At 24 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at rest at 48h(At 48 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at rest at 72h(At 72 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at movement at 12h(At 12 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at movement at 24h(At 24 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at movement at 48h(At 48 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at movement at 72h(At 72 hours after extubation)
- Time weaned to spontaneous breathing(within 48 hours after surgery)
- Exutubation time(within 72 hours after surgery)
- Patient satisfaction to pain management at 12 hours(At 12 hours after surgery)
- Patient satisfaction to pain management at 24 hours(At 24 hours after surgery)
- Patient satisfaction to pain management at 48 hours(At 48 hours after surgery)
- Patient satisfaction to pain management at 72 hours(At 72 hours after surgery)
- Postoperative nausea or vomiting(Within 72 hours after surgery)
- Length of stay in hospital(Within 30 days after surgery)
- chronic postsurgical pain at 1 month(At 1 month after surgery)
- surgical site infection(Within 30 days after surgery)
- chronic postsurgical pain at 6 month(At 6 months after surgery)
- chronic postsurgical pain at 12 month(At 12 months after surgery)
- Brief Pain Inventory (BPI) at 1 month(At 1 month after surgery)
- Brief Pain Inventory (BPI) at 3 month(At 3 month after surgery)
- Brief Pain Inventory (BPI) at 6 month(At 6 month after surgery)
- Brief Pain Inventory (BPI) at 12 month(At 12 month after surgery)
- Neuropathic Pain Questionnaire (NPQ) at 1 month(At 1 month after surgery)
- Neuropathic Pain Questionnaire (NPQ) at 3 month(At 3 month after surgery)
- Neuropathic Pain Questionnaire (NPQ) at 6 month(At 6 month after surgery)
- Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) at 1 month(At 1 month after surgery)
- Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) at 6 month(At 6 month after surgery)
- Neuropathic Pain Questionnaire (NPQ) at 12 month(At 12 month after surgery)
- Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) at 3 month(At 3 month after surgery)
- Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) at 12 month(At 12 month after surgery)
- Quality of Recovery Questionnaire (QoR-15)(At 72 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at rest at 12h(At 12 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at rest at 24h(At 24 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at rest at 48h(At 48 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at rest at 72h(At 72 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at movement at 12h(At 12 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at movement at 24h(At 24 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at movement at 48h(At 48 hours after extubation)
- Numerical Rating Scale (NRS) pain scores at movement at 72h(At 72 hours after extubation)
- Patient-controlled analgesia machine morphine consumption at 12h(At 72 hours after extubation)
- Time for the first dose of morphine as recorded on patient-controlled analgesia machine(Within 48 hours after surgery)
- Time weaned to spontaneous breathing(within 48 hours after surgery)
- Exutubation time(within 72 hours after surgery)
- Patient satisfaction to pain management at 12 hours(At 12 hours after surgery)
- Postoperative nausea or vomiting(Within 72 hours after surgery)
- Length of stay in ICU(Within 1 week after surgery)
- Patient satisfaction to pain management at 24 hours(At 24 hours after surgery)
- Patient satisfaction to pain management at 72 hours(At 72 hours after surgery)
- Proteomics analysis(Within 72 hours after surgery)
- Patient satisfaction to pain management at 48 hours(At 48 hours after surgery)
- Oral analgesic use(Within 72 hours after surgery)
- Length of stay in hospital(Within 30 days after surgery)
研究者
WONG MAN KIN
Assistant Professor
Chinese University of Hong Kong