Potential Benefit of the Combination of Metamizole and Ibuprofen After Third Lower Molar Extraction

Study Overview
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Brief Summary
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Postoperative pain is common and particularly outpatients may experience unsatisfactory pain relief. This randomized, double-blind, crossover study of postoperative pain in outpatients undergoing split-mouth, third lower molar extraction aims to examine whether or not the combination of metamizole and ibuprofen is superior to either drug alone.

Official Title
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Potential Benefit of the Combination of Metamizole and Ibuprofen After Third Lower Molar Extraction

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Metamizole and Ibuprofen
* Drug: Metamizole and Placebo
* Drug: Ibuprofen and Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: planned sequential both-sided lower third molar extraction (split-mouth) with osteotomy (with or without upper molar extraction in local anesthesia) able to understand the study and the NRS scale Exclusion Criteria: simultaneous both sided extraction or only upper third molar extraction general anesthesia known or presumed abnormal coagulation status known or presumed liver or renal dysfunction contraindication against metamizole known or suspected (known or suspected allergy against novalgin or other pyrazolones, anaphylactic reaction against NSAIDS, decreased bone marrow function or hematopoesis, hepatic porphyria, glucose-6-phosphate dehydrogenase deficiency, and pregnancy/breastfeeding) contraindication against ibuprofen (known or suspected allergy against ibuprofen, anaphylactic reaction against Nonsteroidal anti-inflammatory drugs (NSAID), active or recurrent stomach or duodenal ulcera or bleeding, severe liver or renal insufficiency, inflammatory bowel syndrome, and pregnancy/breastfeeding) pregnancy and breast feeding mothers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metamizole and Ibuprofen<br>all patients (n=42) will receive metamizol and ibuprofen in one session. In the other session half will receive metamizol and placebo (n=21) and the other half will receive ibuprofen and placebo. The order will be randomized (balanced). | Drug: Metamizole and Ibuprofen<br>* Metamizole (1000mg) plus Ibuprofen (400mg) 15 minutes prior to surgery, at 6 postoperative hours, and at 12 postoperative hours<br>|
| Active Comparator: Metamizole and Placebo<br>This is one of the two comparators for the Arm Metamizol and Ibuprofen. n=21 | Drug: Metamizole and Placebo<br>* Metamizole (1000mg) plus placebo 15 minutes prior to surgery, at 6 postoperative hours, and at 12 postoperative hours<br>|
| Active Comparator: Ibuprofen and Placebo<br>This is the second of the two comparators for the Arm Metamizol and Ibuprofen. n=21 | Drug: Ibuprofen and Placebo<br>* Ibuprofen (400mg) plus placebo 15 minutes prior to surgery, at 6 postoperative hours, and at 12 postoperative hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| area under the curve for pain in the first 12 postoperative hours | The primary outcome is the area under the curve for pain in the first 12 postoperative hours, as assessed by the numeric rating scale | first 12 postoperative hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| area under the curve for pain in the first 18 postoperative hours | This secondary outcome is the area under the curve for pain in the first 18 postoperative hours, as assessed by the numeric rating scale (NRS) | first 18 postoperative hours | 
| highest pain score | This secondary outcome is the highest pain score registered during the observation period, as assessed by the numeric rating scale | total observation period (maximum 18 hours) | 
| night time pain | This secondary outcome is the overall pain during the first night after the intervention, as assessed by the numeric rating scale | first night after the intervention | 
| need for and timing of rescue medication | This secondary outcome is the marked yes or no, depending on whether a rescue medication (extra pain medication) was needed or not | total observation period (maximum 18 hours) | 
| haemorrhage requiring intervention | This secondary outcome is the marked yes or no, depending on whether an intervention to stop haemorrhage was needed or not | total observation period (maximum 18 hours) |