Dose-finding Study of Intrathecal Paracetamol Administered Immediately Before Spinal Anaesthesia With Chloroprocaine HCl 1% for Elective Knee Procedures of Short Duration
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sintetica SA
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Pain Intensity at Rest Evaluated Using a 0-100 mm VAS
研究概览
简要总结
This is a phase II, single centre, randomised, parallel-group, double-blind, three doses, placebo-controlled, exploratory efficacy and safety study. The objective of this study is to investigate the efficacy and safety of a single intrathecal injection of Paracetamol 3% (30 mg/mL) administered at 3 doses to 3 active treatment groups, as compared to placebo, for post-operative analgesia in knee procedures up to 40 min duration performed under spinal anaesthesia with Chloroprocaine HCl 1%.
详细描述
Eligible patients undergoing elective short-duration knee procedures up to 40 min duration will be randomised into 4 treatment groups (15 patients per group) to receive either one of the 3 single doses of Paracetamol 3% (D1: 30 mg, D2: 60 mg, D3: 90 mg) or the placebo solution (P: 0.9% saline solution) by intrathecal injection (IT), according to the randomised, parallel-group design.
Immediately after IT paracetamol or placebo administration, all patients will receive a single IT dose of Chloroprocaine HCl 1% (Non-investigational medicinal product, NIMP) according to the Summary of Product Characteristics indications. The time interval between paracetamol IT and chloroprocaine IT injections should not exceed 2 min.
The study will include a screening phase (Visit 1, Day -21/-1), a treatment phase (IMP IT administration, anaesthesia and surgical procedure: Visit 2, Day 1) and a follow-up phase including an observation period (Visit 3), a final visit and two follow-ups (24 h post-dose and day 7±1).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The study will be double-blind. Neither the Investigator/co-investigators/study nurses involved in the clinical study procedures, nor will the patients be aware of the administered treatment. At the site, syringes for injection will then be prepared by a person not involved in any other study-related activities where a bias is possible.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent: signed written informed consent before inclusion in the study
- •Sex, age and surgery: male/female patients, 18-80 years old (inclusive), scheduled for short duration (up to 40 min) knee procedures
- •Body Mass Index (BMI): 18 - 32 kg/m2 inclusive
- •ASA physical status: I-III
- •Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study.
排除标准
- •Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study. Contraindications to spinal anaesthesia. History of neuromuscular diseases to the lower extremities
- •ASA physical status: IV-V
- •Further anaesthesia: patients expected to require further anaesthesia
- •Allergy: ascertained or presumptive hypersensitivity to the active principles (paracetamol and/or ester type anaesthetics) and/or formulations' ingredients or related drugs, non-steroidal anti-inflammatory drugs and/or opioid derivatives; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers could affect the outcome of the study
- •Chronic pain syndromes: patients with chronic pain syndromes taking opioids, anticonvulsant agents or chronic analgesic therapy
- •Pain assessment: patients anticipated to be unable to make a reliable self-report of pain intensity
- •Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study; ascertained psychiatric and neurological diseases, sepsis, blood coagulation disorders, severe cardiopulmonary disease, thyroid disease, diabetes, other neuropathies, history or evidence of heart failure. History of severe head trauma that required hospitalisation, intracranial surgery or stroke within the previous 30 days, or any history of intracerebral arteriovenous malformation, cerebral aneurism or CNS mass lesion
- •Medications: medication known to interfere with the extent of spinal blocks for 2 weeks before the start of the study. Paracetamol formulations, other than the investigational product, for 2 weeks before the start of the study and during the study. Hormonal contraceptives for females are allowed. Anti-hypotensive, anti-bradycardia (e.g. ephedrine, atropine, Ringer's solution), anti-haemetic and anti-nausea medications will be allowed
- •Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
- •Drug, alcohol: history of drug or alcohol abuse according to the Investigator's opinion
- •Pregnancy and lactation: positive pregnancy test at screening (if applicable), pregnant or lactating women [The pregnancy test will be performed to all fertile women and to all women up to 55 years old, if not in proven menopause (available laboratory test confirming menopause or surgically sterilised)]
研究组 & 干预措施
30 mg Paracetamol 3% (1 mL)
30 mg Paracetamol 3% (1 mL), solution for injection, single dose by intrathecal injection (IT)
干预措施: 30 mg Paracetamol 3% (1 mL) (Drug)
60 mg Paracetamol 3% (2 mL)
60 mg Paracetamol 3% (2 mL), solution for injection, single dose by intrathecal injection (IT)
干预措施: 60 mg Paracetamol 3% (2 mL) (Drug)
90 mg Paracetamol 3% (3 mL)
90 mg Paracetamol 3% (3 mL), solution for injection, single dose by intrathecal injection (IT)
干预措施: 90 mg Paracetamol 3% (3 mL) (Drug)
Placebo, 0.9% saline solution
Placebo, 0.9% saline solution (1 mL, 2 mL or 3 mL), solution for injection, single dose by intrathecal injection (IT)
干预措施: Placebo, 0.9% saline solution (Drug)
结局指标
主要结局
Pain Intensity at Rest Evaluated Using a 0-100 mm VAS
时间窗: Pain intensity at rest evaluated using a 0-100 mm VAS at baseline (within 30 min before NIMP IT injection, 0 h), 1, 1.25, 1.5, 1.75, 2 h after NIMP IT injection, then every 30 min after NIMP IT injection until eligibility for home discharge.
The study primary efficacy measures will be the VAS scores at each predefined time-point after the anaesthetic intrathecal injection until eligibility for home discharge ( VAS scale is 0-100 mm, where 0 is no pain and 100 is maximum pain)
次要结局
- Pain at Rest AUCt1-t2(Up to 4 hours after injection)
- Pain at Rest AUClast(Up to 24 hours after injection)
- Time to First Postoperative Analgesia (Level 1 or 2)(Up to 24 hours after surgery)
- Partecipants to Received Level 1 Analgesia(from surgery day to 24 hours after surgery)
- Partecipants Received Level 2 Analgesia(from surgery day to 24 hours after surgery)
- Total Number of Partecipants Receiving Analgesic 1(From surgery day to 24 hours after surgery)
- Total Number of Partecipants Receiving Analgesic 2(from surgery day to 24 hours after surgery)
- Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End(Form surgery day to 2 hours after surgery end)
- Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End(from surgery day to 4 hours after surgery end)
- Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge(from surgery day to 24 hours after surgery)
- Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia(from surgery day to 24 hours after surgery)
- Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge(from surgery day to 24 hours after surgery)
- Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge(from surgery day to 24 hours after surgery)
- Percentage of Patients Requiring Rescue Anaesthesia(from surgery day to 1 hour after injection)
- Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery)(Up to 20 minutes after injection)
- Maximum Sensory Block(Intraoperative)
- Time to Sensory Block(Intraoperative)
- Time to Regression of Spinal Block(Up to 4 hours after injection)
- Time to Ambulation(Up to 24 hours after injection)
- Time to First Urine(Up to 24 hours after injection)
- Time to Eligibility for Discharge(Up to 24 hours after injection)