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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Efficacy of Paracetamol in Addition to Morphine to Improve Analgesia in the Emergency Department: a Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Analgesia

Intervention / Treatment
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* Drug: Paracetamol
* Drug: Placebo
* Drug: Morphine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol<br>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<br>* s. above<br>* Other names: Paracetamol Sintetica;Drug: Morphine<br>* s. above<br>* Other names: Morphine Sintetica;|
| Placebo Comparator: Placebo<br>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<br>* s. above<br>* Other names: NaCl 0.9%;Drug: Morphine<br>* s. above<br>* Other names: Morphine Sintetica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the total dose of morphine till pain < 4 on the NRS (0-10) after the first infusion of paracetamol or placebo. |  | up to 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of time interval of pain < 4 on the NRS (after been achieved) |  | up to 4 hours | 
| Total dose of morphine within the first 4 hours after the first infusion of paracetamol or Placebo. |  | up to 4 hours | 
| Prevalence of morphine adverse reactions within the first 4 hours after infusion of paracetamol or placebo |  | up to 4 hours, respectively in case of serious adverse events up to recovery time of the patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paracetamol, Morphine