Efficacy of Paracetamol in Addition to Morphine to Improve Analgesia in the Emergency Department (ParaMoED)

• ClinicalTrials.gov Identifier: NCT03843281
• Recruitment Status: Completed
• First Posted: February 18, 2019
• Last Update Posted: October 19, 2020
• Sponsor: Bruno Minotti
• Information provided by (Responsible Party): Bruno Minotti, Cantonal Hospital of St. Gallen

Study Description

Brief Summary:

The purpose of this study is to test the additional effect of paracetamol in combination with morphine for analgesia, respectively to test/confirm an opioid sparing effect due to the additional use of Paracetamol, as well as the reduction of adverse drug reactions of morphine.

Condition or disease	Intervention/treatment	Phase
Analgesia	Drug: Paracetamol; Drug: Placebo; Drug: Morphine	Phase 4

Detailed Description:

Paracetamol (acetaminophen) is widely used around the world for mild to moderate pain in all age groups. Prescription at the emergency department is very common and some studies suggest the use in alternative of Morphine, at least in the renal colic.

Morphine has also a complex analgesic effect due to inhibition of µ Receptors in the central nervous system and in the dorsal horn of the spinal cord. Morphine (like other opioids) is accepted as a cornerstone of acute pain management in the emergency department. However, occurrence of adverse drug reactions is up to 25%, mainly nausea and drowsiness.

The use of paracetamol in addition to morphine showed in a meta-analysis in the post-operative setting an opioid sparing effect of 20% over the first postoperative 24 hours, but did not change the incidence of morphine-related adverse effects in the postoperative period. An additive effect was showed of the two medicaments in another Study measuring the median effective analgesic dose (ED50).

The purpose of this study is to test the additional effect of paracetamol in combination with morphine for analgesia, respectively to test/confirm an opioid sparing effect due to the additional use of Paracetamol, as well as the to reduction of adverse drug reactions of morphine.

The study is a multicenter, randomized, double-blind, placebo-controlled. We randomize patients with pain-score >=4 on a pain Scala of 0-10 Points (numeric rating scale) in two group, one with paracetamol, one with placebo to investigate the (additive) effect of paracetamol in combination with morphine. The treatment team and the patients will be blinded to the administration. The study design is outlined to confirm the result of previous studies who stated a 20% reduction of morphine doses when combined with paracetamol. Study duration for each patient would be 240 min.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 222 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Paracetamol in Addition to Morphine to Improve Analgesia in the Emergency Department: a Multicenter, Randomized, Double-blind, Placebo-controlled Trial
• Actual Study Start Date: May 2, 2019
• Actual Primary Completion Date: October 15, 2020
• Actual Study Completion Date: October 15, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Paracetamol; Paracetamol 1 g (100 mL) IV + Morphine 0.1 mg/kg IV (repeatable in Doses of 0.05 mg/kg), 100 patients over 4 hours	Drug: Paracetamol; s. above; Other Name: Paracetamol Sintetica; Drug: Morphine; s. above; Other Name: Morphine Sintetica
Placebo Comparator: Placebo; Placebo (NaCl 0.9% 100 mL IV) + Morphine 0.1 mg/kg IV (repeatable in Doses of 0.05 mg/kg), 100 patients over 4 hours	Drug: Placebo; s. above; Other Name: NaCl 0.9%; Drug: Morphine; s. above; Other Name: Morphine Sintetica

Outcome Measures

Primary Outcome Measures :

1. Assessment of the total dose of morphine till pain < 4 on the NRS (0-10) after the first infusion of paracetamol or placebo. [ Time Frame: up to 4 hours ]

Secondary Outcome Measures :

1. Assessment of time interval of pain < 4 on the NRS (after been achieved) [ Time Frame: up to 4 hours ]
2. Total dose of morphine within the first 4 hours after the first infusion of paracetamol or Placebo. [ Time Frame: up to 4 hours ]
3. Prevalence of morphine adverse reactions within the first 4 hours after infusion of paracetamol or placebo [ Time Frame: up to 4 hours, respectively in case of serious adverse events up to recovery time of the patient ]

Other Outcome Measures:

1. Maximal Dose of Morphine based on adverse events [ Time Frame: up to 4 hours ]
   A maximal Dose of opioids has been defined in our daily practice and in several guidelines with a precise number (e.g. 20 mg/4 h). In this trial we will use instead a maximal Dose defined with clinical criteria (GCS < 13, SpO2 < 90% with 4 L/min O2, uncontrolled vomiting). Assessment intended as occurrence of adverse events of the application of a such algorithms will be outcome of interest (not a secondary outcome because absence of a control group)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient with pain with Pain-score is more or equal than four in a numeric rating scale from zero to ten (i.e. indication for a treatment with morphine)
• Age over 18
• Signed informed consent. In case, patient is not able to sign the informed consent due to pain, at least verbal consent has to be provided. After pain relief, written informed consent with data and time has to be obtained

Exclusion Criteria:

• Analgesia in the past last 6 hours prior to visit at the emergency department
• Current Analgesia with long-acting/extended-release drugs
• Current Analgesia with opioids
• Chronic pain syndrome
• Contraindication for either paracetamol or morphine
• Patient's refusal of paracetamol or morphine treatment
• Pregnancy or Breastfeeding
• GCS < 13
• SpO2 < 90% with a maximum of 4 L/Min O2
• Systolic Blood Pressure < 90 mmHg
• "Fast Track"/Notfallpraxis patients

Contacts and Locations

Locations

Switzerland

Kantonsspital St.Gallen

Sankt Gallen, Switzerland, 9007

Sponsors and Collaborators

Bruno Minotti

More Information

• Responsible Party: Bruno Minotti, Sponsor-Investigator, Cantonal Hospital of St. Gallen
• ClinicalTrials.gov Identifier: NCT03843281
• Other Study ID Numbers: CTU17.014
• First Posted: February 18, 2019
• Last Update Posted: October 19, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Bruno Minotti, Cantonal Hospital of St. Gallen:

Paracetamol; Morphine

Additional relevant MeSH terms:

Emergencies; Disease Attributes; Pathologic Processes; Acetaminophen; Morphine; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Analgesics, Non-Narcotic; Antipyretics