Clinical trial NCT03428230: Intrathecal Paracetamol Before Spinal Anaesthesia With Chloroprocaine HCl 1% for Short Knee Procedures
Official title: Dose-finding Study of Intrathecal Paracetamol Administered Immediately Before Spinal Anaesthesia With Chloroprocaine HCl 1% for Elective Knee Procedures of Short Duration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain, Postoperative
Lead sponsor: Sintetica SA
Sponsor class: INDUSTRY
Collaborators: name: Cross Research S.A.
First posted: 2018-02-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients will be randomised into four treatment groups (15 patients/group) to receive either one of the three single doses of Paracetamol 3% (30 mg, 60 mg, 90 mg) or placebo solution (1 mL, 2 mL, 3 mL) according to the randomised, parallel-group design.
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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%.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. Informed consent: signed written informed consent before inclusion in the study
2. Sex, age and surgery: male/female patients, 18-80 years old (inclusive), scheduled for short duration (up to 40 min) knee procedures
3. Body Mass Index (BMI): 18 - 32 kg/m2 inclusive
4. ASA physical status: I-III
5. 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.

Exclusion Criteria:

1. 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
2. ASA physical status: IV-V
3. Further anaesthesia: patients expected to require further anaesthesia
4. 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
5. Chronic pain syndromes: patients with chronic pain syndromes taking opioids, anticonvulsant agents or chronic analgesic therapy
6. Pain assessment: patients anticipated to be unable to make a reliable self-report of pain intensity
7. 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
8. 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
9. 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
10. Drug, alcohol: history of drug or alcohol abuse according to the Investigator's opinion
11. Pregnancy and lactation: positive pregnancy test at screening (if applicable), pregnant or lactating women \[The pregnancy test will be performed to all fertile women and to all women up to 55 years old, if not in proven menopause (available laboratory test confirming menopause or surgically sterilised)\]

Primary outcomes:
measure: Pain Intensity at Rest Evaluated Using a 0-100 mm VAS
timeFrame: 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.
Secondary outcomes:
measure: Pain at Rest AUCt1-t2
timeFrame: Up to 4 hours after injection
measure: Pain at Rest AUClast
timeFrame: Up to 24 hours after injection
measure: Time to First Postoperative Analgesia (Level 1 or 2)
timeFrame: Up to 24 hours after surgery
measure: Partecipants to Received Level 1 Analgesia
timeFrame: from surgery day to 24 hours after surgery
measure: Partecipants Received Level 2 Analgesia
timeFrame: from surgery day to 24 hours after surgery
measure: Total Number of Partecipants Receiving Analgesic 1
timeFrame: From surgery day to 24 hours after surgery
measure: Total Number of Partecipants Receiving Analgesic 2
timeFrame: from surgery day to 24 hours after surgery
measure: Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End
timeFrame: Form surgery day to 2 hours after surgery end
measure: Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End
timeFrame: from surgery day to 4 hours after surgery end
measure: Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge
timeFrame: from surgery day to 24 hours after surgery
measure: Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge
timeFrame: from surgery day to 24 hours after surgery
measure: Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge
timeFrame: from surgery day to 24 hours after surgery
measure: Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia
timeFrame: from surgery day to 24 hours after surgery
measure: Percentage of Patients Requiring Rescue Anaesthesia
timeFrame: from surgery day to 1 hour after injection
measure: Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery)
timeFrame: Up to 20 minutes after injection
measure: Maximum Sensory Block
timeFrame: Intraoperative
measure: Time to Sensory Block
timeFrame: Intraoperative
measure: Time to Regression of Spinal Block
timeFrame: Up to 4 hours after injection
measure: Time to Ambulation
timeFrame: Up to 24 hours after injection
measure: Time to First Urine
timeFrame: Up to 24 hours after injection
measure: Time to Eligibility for Discharge
timeFrame: Up to 24 hours after injection
Other outcomes:
measure: Number of Participants With Neurological Complications Including TNS
timeFrame: From anaesthetic intrathecal injection up to day 7±1 (i.e. 6±1 days after analgesic/anaesthetic IT injection and surgery)
Locations:
city: Gravesano
country: Switzerland
facility: Department of Anaesthesiology, Clinica Ars Medica
Study officials:
affiliation: Department of Anaesthesiology, Clinica Ars Medica, Via Cantonale, CH-6929 Gravesano, Switzerland
name: Claudio Camponovo, MD
role: PRINCIPAL_INVESTIGATOR
References: