Application Research of Hydromorphinone Sustained-release Tablets in the Treatment of Elderly Patients With Cancer Pain Accompanied by Renal Insufficiency
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- The changes in estimated glomerular filtration rate (eGFR) from baseline at the end of the 4th week of treatmentDetailed
研究概览
简要总结
This clinical study aims to understand whether domestic hydromorphinone sustained-release tablets are effective and safe in treating moderate to severe cancer pain in elderly patients with renal insufficiency.
It will also understand key safety concerns, especially regarding renal function and neurotoxicity.
The main questions it aims to answer include:1. Can hydromorphinone sustained-release tablets effectively relieve the pain of such patients and improve their quality of life?2. During the treatment period, what effect does this drug have on renal function (measured by eGFR)? 3. In this specific population, what are the occurrence and characteristics of neurotoxicity and other side effects induced by opioids? Researchers will compare elderly cancer pain patients with renal insufficiency with those with normal renal function (both receiving the study drug treatment) to observe whether there are differences in efficacy and safety results.
Participants will:
Receive a standardized treatment plan: First, subcutaneous injection of hydromorphinone injection for dose titration, and then switch to daily oral administration of hydromorphinone sustained-release tablets for 4 weeks.
Visit the clinic for assessment and examination (including renal function tests) during the baseline period, on the 7th day, and at the weekends of the 2nd, 3rd, and 4th days.
Regularly monitor and record the degree of pain, the occurrence of explosive pain, the use of medication, and any side effects.
详细描述
- The research background and principle of elderly cancer patients are often faced with moderately severe pain, the pain management is particularly complex in this group. The physiological functions of the elderly decline, often accompanied by a decrease in renal function, which significantly limits the safe use of many standard opioid analgesics, such as morphine. The active metabolites of morphine tend to accumulate in patients with renal insufficiency, increasing the risk of neurotoxicity. Another commonly used drug, oxycodone, may cause a relatively high incidence of gastrointestinal adverse reactions. Hydromorphinone is a potent opioid drug, and its pharmacological properties may offer a solution to this predicament. It is mainly metabolized through liver glucoaldehyde acidification, generating inactive metabolites, and does not rely on the complex cytochrome P450 enzyme system. Therefore, the risk of drug interactions is relatively low, and theoretically, it has a smaller impact on kidney function, especially suitable for elderly patients with reduced kidney function. However, although there have been some studies on imported hydromoradone preparations, domestic hydromoradone hydrochloride sustained-release tablets (such as Ruining ®) have lacked prospective and systematic clinical evidence in the cancer pain population characterized by dual risk factors of "old age" and "renal insufficiency" since their launch. This study aims to fill this crucial gap in evidence.
- The research design and methodology described in this study using prospective, observational cohort design. Unlike randomized controlled trials, this study aims to observe the natural outcomes of standardized treatment regimens in elderly patients with different renal function statuses under real-world conditions. All eligible patients enrolled in the group will receive a unified analgesic treatment plan based on international authoritative guidelines: Firstly, subcutaneous injection titration of hydromorphinone injection will be performed to quickly determine the individualized dose required for pain control; After the pain stabilized, it was uniformly converted to the same dose of domestic hydromorphinone sustained-release tablets for oral maintenance treatment once daily. The total treatment observation period was 4 weeks.
The key to the research lies in "hierarchical comparison". Before treatment, the investigators will naturally divide the patients into two cohorts based on their estimated glomerular filtration rate (eGFR, a core indicator for evaluating renal function) : the "Elderly with renal insufficiency group" and the "Elderly with normal renal function Group". In this way, the investigators can directly compare the performance differences of the drug in these two types of people with different physiological states.
The sample size calculation (planned to include a total of 62 patients) was based on the primary safety endpoint - the change in eGFR values relative to baseline at week 4 of treatment. A clinically significant effect size was preset during the calculation, and sufficient statistical certainty was ensured to guarantee the reliability of the research results. 3. The core assessment and monitoring framework in addition to conventional pain intensity assessment (NRS) adopting digital grading method, quality of living survey and common adverse reactions, this research established dual core security monitoring system:
Dynamic monitoring of renal function: Serum creatinine will be systematically detected and eGFR calculated at five time points before and during treatment. This is not only used to compare the differences between groups, but more importantly, to monitor the dynamic trajectory of each patient's individual renal function and promptly detect any clinically significant signs of deterioration.
Active screening for neurotoxicity (OIN) : In response to neurotoxic symptoms such as delirium, drowsiness, and myoclonus that may be caused by opioids, the study will conduct active screening and assessment once a week using a series of standardized scales, for example, using the Confusion Assessment method (CAM) to screen for delirium. This systematic monitoring aims to capture the incidence and characteristics of OIN more precisely. 4. Data analysis, statistical analysis strategy will use advanced statistical models to cope with the complexity of clinical data. For the primary endpoint (eGFR change), covariance analysis will be used to correct for baseline eGFR differences during statistical analysis, thereby more purer assessing the impact of the treatment itself on renal function. For data such as pain scores that are repeatedly measured at different time points, generalized estimating equations will be used for analysis to effectively utilize all the information of the longitudinal data. Furthermore, if a sufficient number of neurotoxic events are observed in the study, the investigators will conduct an exploratory analysis and attempt to construct a clinical risk prediction tool (nomogram) using a multi-factor regression model to identify high-risk patients with OIN. 5. The risk control and clinical patient safety is the primary consideration. The research protocol is equipped with clear safety suspension rules: once a patient's eGFR drops by more than 30% from baseline or falls within the range of severe renal failure, the study medication will be immediately suspended and a multidisciplinary consultation will be initiated. For patients with moderate to severe neurotoxicity, there are already pre-established alternative analgesic regimens (such as switching to fentanyl transdermal patches). The entire research was carried out on the "Standardized Cancer Pain Treatment Demonstration Ward" platform of Tai 'an Cancer Hospital. This team has mature cancer pain management and emergency response procedures. 6. The value of the research and production in this study beyond the simple answer of "analgesia is effective", focus on "in the vulnerable groups is safe" more pressing clinical problem. Its achievements are expected to provide value on three levels:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 65 years.
- •Pathologically or cytologically confirmed malignant tumor.
- •Opioid-naïve patients with moderate-to-severe cancer pain (Numerical Rating Scale score ≥ 4).
- •Renal function meeting one of the following criteria at baseline:
- •1）Mild-to-moderate renal insufficiency group: 30 mL/min/1.73m² ≤ estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m².
- •2）Normal renal function group: eGFR ≥ 90 mL/min/1.73m². 5.Expected survival period ≥ 3 months. 6.Ability to take oral medication and cooperate with study assessments. 7.Willing to participate voluntarily and able to provide signed informed consent.
排除标准
- •Severe renal insufficiency (eGFR < 30 mL/min/1.73m²) or requirement for renal replacement therapy.
- •Severe hepatic insufficiency (alanine aminotransferase / aspartate aminotransferase ≥ 2.5 times the upper limit of normal or Child-Pugh Class C).
- •Paralytic ileus.
- •Pain of unclear origin or pain that is solely acute/incident pain.
- •Symptoms or history of diseases such as intracranial hypertension, head injury, cerebral aneurysm, or other central nervous system disorders.
- •Symptoms of prostatic hypertrophy, thyroid dysfunction, or urethral stricture. Symptoms of asthma, respiratory obstruction, or respiratory failure.
- •Known allergy or hypersensitivity to hydromorphone or oxycodone.
- •Use of monoamine oxidase inhibitors within 14 days prior to enrollment.
- •Participation in any other clinical trial within 1 month prior to enrollment.
- •Any other condition considered by the investigator as unsuitable for participation in this study.
研究组 & 干预措施
Hydromorphone - Renal Insufficiency Group
Elder cancer pain patients with mild to moderate renal insufficiency at enrollment, defined by an estimated glomerular filtration rate (eGFR) range of 30 ≤ eGFR < 90 mL/min/1.73m². They receive standardized Hydromorphone Sustained-Release Tablet treatment.
Hydromorphone - Normal Renal Function Group
Elder cancer pain patients with normal renal function at enrollment, defined by an estimated glomerular filtration rate (eGFR) of eGFR ≥ 90 mL/min/1.73m². They receive the identical standardized Hydromorphone Sustained-Release Tablet treatment as Cohort 1, serving as the reference comparison group.
结局指标
主要结局
The changes in estimated glomerular filtration rate (eGFR) from baseline at the end of the 4th week of treatmentDetailed
时间窗: From the start of maintenance treatment with hydromorphinone sustained-release tablets until the end of the fourth week of treatment.
The estimated glomerular filtration rate (eGFR) is a validated indicator of kidney function. It is calculated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which incorporates the patient's age and sex. All values are normalized to body surface area and expressed as mL/min/1.73m². On this scale, higher eGFR values indicate better kidney function, while lower values indicate impaired kidney function. The change in eGFR is defined as the value measured at week 4 minus the value measured at baseline (immediately prior to treatment initiation). A negative change value indicates a decrease in eGFR from baseline, representing a decline in kidney function. A positive change value indicates an increase in eGFR from baseline, representing an improvement in kidney function. eGFR is measured from venous blood samples collected at baseline and at week 4.
次要结局
未报告次要终点
研究者
Xian'guo Wang
Chief Physician
Taian Cancer Hospital