An Open, Randomised, Parallel Group Controlled, Single Centre Safety Study to Assess the Safety and Efficacy of Tri-Solfen in Providing Anaesthesia Prior to Surgical Debridement of Leg Ulcers and Post-operative Pain Relief
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Lidocaine Maximum Plasma Concentration
研究概览
简要总结
This is a Phase IIa open, randomised, single and parallel group, therapy controlled, single centre study, which has been divided into 3 sequential phases, which are designed to study respectively, (a) the time taken to achieve surface anaesthesia, (b) the extent of post-operative pain relief and (c) the depth and quality of anaesthesia during a leg ulcer surgical debridement procedure
详细描述
As part of the study, patients with leg ulcers (venous, arterial, mixed aetiology or lymphoedema) requiring surgical debridement will attend 4 visits to the study centre (Day 0, Day 1, Day 7 and Day 14). After informed consent and screening for inclusion / exclusion criteria patients will be managed as follows:
Phase 1 (N=10 patients): This is a pilot (non-comparative) phase designed to assess safety, pharmacokinetics and achievement of clinically acceptable levels of surface analgesia for Tri-Solfen in the intended patient population, prior to surgical wound debridement. Prior to surgical debridement all patients will have a single application of the Tri-Solfen product 2mL/10cm2 wound area) administered. The product will be allowed to remain in contact with the wound bed for 1 minute and surface anaesthesia will then be tested by needle-stick for up to 30 minutes after application (at 1, 3, 5, 10, 20 and 30 minutes, i.e. testing will stop when the needle stick can no longer be felt). In parallel serial blood draws of 10mL will be taken at 2min, 30min, 1 hr, 2hrs and 6hrs after application to determine systemic absorption of lidocaine and bupivacaine.
Surgical debridement will proceed after a needle stick can no longer be felt and will cease when either the wound bed is deemed to be clean and free from necrotic tissue in the presence of punctate bleeding or where pain increases to an unacceptable level as defined by the patient. Pain assessments will be carried out during the procedure and at 2 min, 30 min, 1 hour, 6 hrs and 24 hours after the procedure is complete.
Phase 2 (N=40 patients; 20 per group): This is a comparative phase of Tri-Solfen vs standard of care in the management of post-operative analgesia. All patients will receive standard of care (i.e. 60 mins of EMLA Cream) to anaesthetise the leg ulcer and will undergo surgical debridement after a needle stick can no longer be felt and will cease when either the wound bed is deemed to be clean and free from necrotic tissue in the presence of punctate bleeding or where pain increases to an unacceptable level as defined by the patient.
On completion of surgical debridement, patients will be randomised to one of two groups:
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
- None
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
- •Male and female patients aged over 18 years of age, with a chronic leg ulcer of arterial, venous, mixed aetiology or lymphoedema willing and able to provide informed consent and comply with study procedures.
- •Presence of slough, necrotic or unhealthy tissue that requires removal by surgical (sharp) debridement
- •Study wound that is 2-30 cm2 in regards surface area and has been present for 1-60 months.
- •Presence of acute, non-cyclic pain experienced by the patient following a previous debridement. A baseline pain score (prior to any administration of treatment) should be >50mm on a 100mm visual analogue scale
排除标准
- •Patients with an acute or chronic infectious skin disease
- •Wound bed with exposed bone, tendon or fascia
- •Patients with any anaesthetic allergy or intolerance of local anaesthetics or hypersensitivity to any of the ingredients of the Tri-Solfen or EMLA product
- •Patients with cellulitis and/or osteomyelitis
- •Patients with porphyria
- •Patients with abnormal thyroid function including thyrotoxicosis
- •Patients with established ventricular fibrillation, cardiac dilatation (severe angina pectoris, obstructive cardiomyopathy), coronary insufficiency, including angina, organic brain disease or atherosclerosis.
- •Patients with clinically significant hepatic or renal insufficiency (glomerular filtration rate <30mL per minute)
- •Patients receiving more than 2 week's treatment with immunosuppressive agents in the past 3 months.
- •Patients receiving oral corticosteroid therapy or topical corticosteroid on the leg where the reference ulcer is located.
- •Any investigational drug use within 30 days
- •Severe malnutrition, as judged by the investigator
- •Patients who, in the opinion of the investigator, have an existing condition that would compromise their partcipation and follow up in this study
- •Patients who have, or are suspected of having any underlying or skin malignancy, or who have received treatment for any active malignancy, apart from non-melanomatic skin cancer, within 3 months prior to treatment.
- •History of radiation at the study site
- •Any other conditions that could impede wound healing
- •Patients receiving concomitant medicines including, Carbemazepines, Rifampicin, Phenytoin, Griseofulvin, Phenobarbitone, and Sulphonylureas
研究组 & 干预措施
Phase 1 open, pilot phase
A pilot group of 10 patients who will receive Tri-Solfen only (non-randomised) once, prior to debridement
干预措施: Tri-Solfen Gel (Lidocaine HCl, Bupivacaine HCl, Adrenaline Acid Tartrate /Cetrimide) (Drug)
Phase 2 - Tri-Solfen
A group of 20 patients who will receive EMLA cream (60 minute application) to anaesthetise the leg ulcer prior to surgical wound debridement, followed on completion of surgery by a single application of Tri-Solfen.
干预措施: Tri-Solfen Gel (Lidocaine HCl, Bupivacaine HCl, Adrenaline Acid Tartrate /Cetrimide) (Drug)
Phase 2 - Tri-Solfen
A group of 20 patients who will receive EMLA cream (60 minute application) to anaesthetise the leg ulcer prior to surgical wound debridement, followed on completion of surgery by a single application of Tri-Solfen.
干预措施: EMLA cream (Drug)
Phase 2 - Standard Care
A group of 20 patients who will receive EMLA Cream (60 minute application) to anaesthetise the leg ulcer prior to surgical wound debridement, followed on completion of surgery by standard of care post-operative analgesia.
干预措施: EMLA cream (Drug)
Phase 2 - Standard Care
A group of 20 patients who will receive EMLA Cream (60 minute application) to anaesthetise the leg ulcer prior to surgical wound debridement, followed on completion of surgery by standard of care post-operative analgesia.
干预措施: Post Operative Analgesia (Paracetamol, Ibuprofen) (Drug)
Phase 3 - Tri-Solfen
A group of 20 patients who will receive two applications of Tri-Solfen (2mL/10cm2), once prior to debridement and once on completion of the procedure.
干预措施: Tri-Solfen Gel (Lidocaine HCl, Bupivacaine HCl, Adrenaline Acid Tartrate /Cetrimide) (Drug)
Phase 3 - Tri-Solfen
A group of 20 patients who will receive two applications of Tri-Solfen (2mL/10cm2), once prior to debridement and once on completion of the procedure.
干预措施: Post Operative Analgesia (Paracetamol, Ibuprofen) (Drug)
Phase 3 - EMLA
A group of 20 patients who will receive EMLA Cream (60-minute application) prior to surgical debridement
干预措施: EMLA cream (Drug)
Phase 3 - EMLA
A group of 20 patients who will receive EMLA Cream (60-minute application) prior to surgical debridement
干预措施: Post Operative Analgesia (Paracetamol, Ibuprofen) (Drug)
结局指标
主要结局
Lidocaine Maximum Plasma Concentration
时间窗: Day 0 - Day 1
Blood draws to determine systemic levels of lidocaine
Bupivacaine Maximum Plasma Concentration
时间窗: Day 0 - Day 1
Blood draws to determine systemic levels of bupivacaine
Local tolerability assessments
时间窗: Day 0 - Day 1
Numerical Rating Scale (0-1) for presence of bleeding and wound infection
次要结局
- Pain on Application(1 minute)
- Time taken to achieve clinically acceptable surface anaesthesia(0-30 minutes after application)
- Pain during wound debridement(10-15 minutes)
- Clinical adequacy of wound debridement(On completion of surgery)
- Duration of post-operative pain relief(Up to 24 hours)