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Pain, PostoperativePhase 2NCT03428230

Intrathecal Paracetamol Before Spinal Anaesthesia With Chloroprocaine HCl 1% for Short Knee Procedures

A Phase 2 study testing 30 mg Paracetamol 3% (1 mL), 60 mg Paracetamol 3% (2 mL) and 90 mg Paracetamol 3% (3 mL) in people with Pain, Postoperative, run by Sintetica SA at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Pain, Postoperative
What is being tested?
30 mg Paracetamol 3% (1 mL), 60 mg Paracetamol 3% (2 mL) and 90 mg Paracetamol 3% (3 mL)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteSwitzerland
Study dates
6 Aug 2018to 22 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 11Show fewer
  • 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)]

Trial locations and contacts

1 site in 1 country.

Switzerland1 site
  • Department of Anaesthesiology, Clinica Ars Medica

    Gravesano, 6929

Other trials in Switzerland

About this study

Official title: Dose-finding Study of Intrathecal Paracetamol Administered Immediately Before Spinal Anaesthesia With Chloroprocaine HCl 1% for Elective Knee Procedures of Short Duration

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%.

Read the 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).

Being tested
30 mg Paracetamol 3% (1 mL), 60 mg Paracetamol 3% (2 mL), 90 mg Paracetamol 3% (3 mL), Placebo, 0.9% saline solution, NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection
Medical subject headings
Pain, Postoperative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 30 mg Paracetamol 3% (1 mL)Drug

    Single administration by intrathecal injection just before spinal anaesthesia. The injection will be performed according to the hospital procedures. For the intrathecal injection of Paracetamol followed by the intrathecal injection of the anaesthetic, two needles will be used: one introducer needle, which will serve to introduce the second needle through the skin, plus one intrathecal Pencil point needle (27-G or 25-Gauge or Reganesth or Nizell needle) to which the first syringe containing Paracetamol will be attached first, followed by the second syringe with the anaesthetic. In this way only one intrathecal puncture will be performed. Lumbar puncture will be done according to the standard hospital procedures.

  • 60 mg Paracetamol 3% (2 mL)Drug

    Single administration by intrathecal injection just before spinal anaesthesia. The injections will be performed according to the hospital procedures. For the intrathecal injection of Paracetamol followed by the intrathecal injection of the anaesthetic, two needles will be used: one introducer needle, which will serve to introduce the second needle through the skin, plus one intrathecal Pencil point needle (27-G or 25-Gauge or Reganesth or Nizell needle) to which the first syringe containing Paracetamol will be attached first, followed by the second syringe with the anaesthetic. In this way only one intrathecal puncture will be performed. Lumbar puncture will be done according to the standard hospital procedures.

  • 90 mg Paracetamol 3% (3 mL)Drug

    Single administration by intrathecal injection just before spinal anaesthesia. The injections will be performed according to the hospital procedures. For the intrathecal injection of Paracetamol followed by the intrathecal injection of the anaesthetic, two needles will be used: one introducer needle, which will serve to introduce the second needle through the skin, plus one intrathecal Pencil point needle (27-G or 25-Gauge or Reganesth or Nizell needle) to which the first syringe containing Paracetamol will be attached first, followed by the second syringe with the anaesthetic. In this way only one intrathecal puncture will be performed. Lumbar puncture will be done according to the standard hospital procedures.

  • Placebo, 0.9% saline solutionDrug

    Also called physiological solution

    Single administration by intrathecal injection just before spinal anaesthesia. The injections will be performed according to the hospital procedures. For the intrathecal injection of Placebo followed by the intrathecal injection of the anaesthetic, two needles will be used: one introducer needle, which will serve to introduce the second needle through the skin, plus one intrathecal Pencil point needle (27-G or 25-Gauge or Reganesth or Nizell needle) to which the first syringe containing Placebo will be attached first, followed by the second syringe with the anaesthetic. In this way only one intrathecal puncture will be performed. Lumbar puncture will be done according to the standard hospital procedures.

  • NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injectionDrug

    Also called Ampres 1%

    Immediately after intrathecal administration of the Paracetamol dose or Placebo, all patients will receive a single intrathecal dose of Chloroprocaine HCl 1% according to the Summary of Product Characteristics indications. Time interval between the 2 administrations should not exceed 2 min.

Study groups in NCT03428230
Study groupRoleWhat they receive
30 mg Paracetamol 3% (1 mL)Experimental30 mg Paracetamol 3% (1 mL), solution for injection, single dose by intrathecal injection (IT)
Receives: Drug: 30 mg Paracetamol 3% (1 mL); Drug: NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection
60 mg Paracetamol 3% (2 mL)Experimental60 mg Paracetamol 3% (2 mL), solution for injection, single dose by intrathecal injection (IT)
Receives: Drug: 60 mg Paracetamol 3% (2 mL); Drug: NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection
90 mg Paracetamol 3% (3 mL)Experimental90 mg Paracetamol 3% (3 mL), solution for injection, single dose by intrathecal injection (IT)
Receives: Drug: 90 mg Paracetamol 3% (3 mL); Drug: NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection
Placebo, 0.9% saline solutionPlacebo comparatorPlacebo, 0.9% saline solution (1 mL, 2 mL or 3 mL), solution for injection, single dose by intrathecal injection (IT)
Receives: Drug: Placebo, 0.9% saline solution; Drug: NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pain Intensity at Rest Evaluated Using a 0-100 mm VAS

    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)

    Measured: 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 (21)
  1. Pain at Rest AUCt1-t2

    AUC t1-t2 is defined as the area under the pain intensity curve at the specified time-intervals

    Measured: Up to 4 hours after injection

  2. Pain at Rest AUClast

    AUClast is defined as the area under the pain intensity curve from 0 h up to the last assessment time

    Measured: Up to 24 hours after injection

  3. Time to First Postoperative Analgesia (Level 1 or 2)

    Postoperatively, patients will be administered an analgesic as needed. Post-operative analgesia could include Ketorolac i.v. [Toradol] 30 mg (level 1 analgesia) and/or Tramadol i.v. 1 mg/kg (level 2 analgesia).

    The administered analgesic (level 1 or 2), analgesic dose and intake frequency will be decided according to the reported surgery-related pain intensity.

    Post-operatively, patients were administered an analgesic, as needed. Post-operative analgesia could include Ketorolac i.v. [Toradol] 30 mg (level 1 analgesia) and/or Tramadol i.v. 1 mg/kg (level 2 analgesia).

    Measured: Up to 24 hours after surgery

  4. Partecipants to Received Level 1 Analgesia

    Partecipants to received Ketorolac i.v. [Toradol] 30 mg administration (level 1 analgesia)

    Measured: from surgery day to 24 hours after surgery

  5. Partecipants Received Level 2 Analgesia

    Partecipants received Tramadol i.v. 1 mg/kg administration (level 2 analgesia)

    Measured: from surgery day to 24 hours after surgery

  6. Total Number of Partecipants Receiving Analgesic 1

    Total number of partecipants receiving Ketorolac i.v. [Toradol] 30 mg

    Measured: From surgery day to 24 hours after surgery

  7. Total Number of Partecipants Receiving Analgesic 2

    Total Number of Partecipants Receiving Tramadol i.v. 1 mg/kg

    Measured: from surgery day to 24 hours after surgery

  8. Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End

    Percentage of patients requiring analgesia (level 1 or level 2) in the first 2 h after surgery end

    Measured: Form surgery day to 2 hours after surgery end

  9. Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End

    Percentage of patients requiring analgesia (level 1 or level 2) in the first 4 h after surgery end

    Measured: from surgery day to 4 hours after surgery end

  10. Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge

    Percentage of patients requiring analgesia (level 1 or level 2) from surgery end until eligibility for home discharge

    Measured: from surgery day to 24 hours after surgery

  11. Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge

    Percentage of patients requiring level 1 analgesia from surgery end until eligibility for home discharge

    Measured: from surgery day to 24 hours after surgery

  12. Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge

    Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Home Discharge

    Measured: from surgery day to 24 hours after surgery

  13. Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia

    Percentage of patients requiring supplementary analgesia, other than the planned level 1 or 2 analgesia

    Measured: from surgery day to 24 hours after surgery

  14. Percentage of Patients Requiring Rescue Anaesthesia

    Percentage of patients requiring rescue anaesthesia

    Measured: from surgery day to 1 hour after injection

  15. Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery)

    Spinal block/Readiness for surgery is defined as the presence of an adequate motor block (Bromage's score ≥ 2) and loss of Pinprick sensation, according to the Investigator's opinion. Time to readiness for surgery is defined as the time from the spinal injection (time 0 h) to achievement of readiness for surgery.

    Measured: Up to 20 minutes after injection

  16. Maximum Sensory Block

    Maximum level of sensory block

    Measured: Intraoperative

  17. Time to Sensory Block

    Time to maximum level of sensory block (bilateral Pinprick test using a 20-G hypodermic needle)

    Measured: Intraoperative

  18. Time to Regression of Spinal Block

    Time period from spinal injection to the complete regression of sensory block to S1.

    Measured: Up to 4 hours after injection

  19. Time to Ambulation

    Time to unassisted ambulation

    Measured: Up to 24 hours after injection

  20. Time to First Urine

    Time to first spontaneous urine voiding

    Measured: Up to 24 hours after injection

  21. Time to Eligibility for Discharge

    Time to eligibility for home discharge

    Measured: Up to 24 hours after injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2018
  2. Study start6 Aug 2018
  3. Primary completion22 Oct 2019
  4. Study completion22 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
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.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03428230
Sponsor's protocol ID
PAR.3-01-2017
Other IDs
CRO-17-133
Status last verified
Jun 2021
First submitted
23 Jan 2018
Last updated
24 Jun 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 30 mg Paracetamol 3% (1 mL), 60 mg Paracetamol 3% (2 mL) and 90 mg Paracetamol 3% (3 mL) in people with Pain, Postoperative, run by Sintetica SA at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pain Intensity at Rest Evaluated Using a 0-100 mm VAS (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2021.

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