Evaluation of the Added Value of Metamizole to Standard Post-operative Treatment After Ambulant Surgery

Study Overview
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Brief Summary
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The aim of this study is to investigate if the addition of metamizole to the standard post-operative treatment, i.e. paracetamol and ibuprofen, is superior in reducing post-operative pain on day 1 after ambulatory surgery compared to the standard post-operative treatment. Therefore, a mono-center, prospective, double-blind, randomized controlled superiority trail will be designed in order to investigate superiority of metamizole compared to the standard post-operative treatment in patients undergoing arthroscopic shoulder surgery.

Detailed Description
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Ambulant surgery has been expanding substantially in the past decade, primarily because it is associated with lower costs and it is believed to be as safe as surgery in the in-patient setting. Moreover, it seems that early discharge can contribute to a faster recovery and a decreased incidence of hospital-associated complications. In view of the relative absence of major complications, post-operative pain and quality of recovery should be considered the principal endpoints after day surgery. The quality of recovery after different types of surgery is of major importance since the evaluation of recovery allows a discrimination between a normal and pathological health trajectory. A disadvantage in the ambulatory setting is related to the absence of postoperative surveillance by professionals. This implicates that the individual patient has to assess, without any support, if his/her quality of recovery is normal or not. There is limited information on procedure-specific quality of recovery after day surgery, however, different tools such as the 1-tem Global Surgical Recovery (GSR) index and the 5-dimensional European Quality of Life (EQ5D) questionnaires can be addressed. Particularly in the ambulant setting, good post-operative analgesia is challenging because patients have to control pain at home by themselves, in the absence of hospital staff. Moreover, there is a limit in the type of analgesia that is available (i.e. no strong opioids) as well as in the route of administration (i.e. no epidural, intravenous, subcutaneous or intramuscular route) at home. Nowadays a multimodal approach to control pain has been advocated in the ambulatory setting. This approach is based on a combination of paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and, if necessary, weak opioids. A local and regional anesthesia also have been advocated in the ambulatory setting to relieve pain for 8 to 24 hours after surgery. Despite this multimodal pain therapy, the prevalence of outpatients suffering moderate to severe acute postoperative pain at home still remains high and varies from 9 to 40%. More specific, patients undergoing haemorrhoid surgery, arthroscopic shoulder and knee surgery, and inguinal hernia repair seem to be at highest risk to develop moderate to severe pain on the fourth postoperative day. Due to this relatively high prevalence and due to the fact that NSAIDs are not always sufficiently effective, can have numerous contraindications and therefore are not suitable in up to 25% of all patients; there is a need for an alternative pain therapy. Metamizole (dipyrone) is a non-opioid compound with strong analgesic, antipyretic and spasmolytic effects. The analgesic efficacy of intravenous or intramuscular metamizole for pain relief after inpatient surgery is well described. Recently, we showed in a prospective, double-blind, randomized controlled trial that the combination of paracetamol and metamizole is equally effective in treatment of acute post-operative pain at home after ambulatory surgery compared to paracetamol and ibuprofen. Moreover, patient satisfaction was equal in both groups, as well as the reported side effects.

Official Title
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Evaluation of the Added Value of Metamizole to Standard Post-operative Treatment After Ambulant Surgery: a Double-blind, Randomized, Controlled Trial

Conditions
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Analgesia, Surgery, Recovery

Intervention / Treatment
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* Drug: Metamizole
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged between 18 and 70 years ASA classification 1,2 or 3 Body weight > 50 kg Undergoing ambulatory arthroscopic shoulder surgery (SAD ± ACJ excision or decompression, decompression + biceps tenodesis, rotator cuff repair, rotator cuff repair + decompression (+ biceps tenodesis) Exclusion Criteria: Not meeting inclusion criteria Patients undergoing SLAP of Bankart repair Cognitive impairment or no understanding of the Dutch language Preoperative pharmacological pain treatment and/or a history of chronic pain Allergy to or contraindication for taking the study medication (e.g. paracetamol, metamizole, ibuprofen or another non-steroidal anti-inflammatory drug) Porphyria Pregnancy or lactation A history of severe renal, hepatic, pulmonary or cardiac failure Current symptoms or a history of gastrointestinal bleeding Ileus or chronic obstipation A history of substance abuse, or use of medication with a suppressive effect on the central nervous system Hypotension Hematological disease Use of anti-rheumatic drugs Rhinosinusitis or nasal polyposis Glucose-6-phosphate dehydrogenase deficiency Fever or other signs of infection Refusal of an interscalene block

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: This trial is designed as a mono-center, prospective, double-blind, randomized placebo controlled superiority trial comparing 2 groups of patients
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metamizole<br>Patients in the experimental group will be instructed to take metamizole 1000 mg orally three times a day for four days, ibuprofen 600 mg orally three times a day for four days and 1000 mg paracetamol orally four times a day during the entire study period. | Drug: Metamizole<br>* Patients in the experimental group will be instructed to take metamizole 1000 mg orally three times a day for four days. All patients will be instructed to take ibuprofen 600 mg orally three times a day for four days and 1000 mg paracetamol orally four times a day during the entire study period.<br>|
| Placebo Comparator: Placebo<br>Patients in the experimental group will be instructed to take a placebo orally three times a day for four days, ibuprofen 600 mg orally three times a day for four days and 1000 mg paracetamol orally four times a day during the entire study period. | Drug: Placebo oral tablet<br>* Patients in the placebo group will be instructed to take a placebo orally three times a day for four days. All patients will be instructed to take ibuprofen 600 mg orally three times a day for four days and 1000 mg paracetamol orally four times a day during the entire study period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain on day 1 | Postoperative pain intensity at movement measured by an 11-point Numeric Rating Scale (NRS) where 0: no pain and 10: worst imaginary pain) on postoperative day 1. | 24 hours after the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of recovery | Quality of Recovery measured by the 1-item Global Surgical Recovery (GSR) index which represents a single question about the extent to which patients consider themselves to be recovered from surgery (0-100%) at baseline and days 7, 14, 28 and 3 months postoperatively. | at baseline and days 7, 14, 28 and 3 months postoperatively. | 
| Quality of recovery | Measured with the EuroQol (EQ5D) questionnaire, which is non-disease specific instrument developed for describing and valuing health-related quality of life, at baseline and days 7, 14, 28 and 3 months postoperatively. | at baseline and days 7, 14, 28 and 3 months postoperatively. | 
| Postoperative pain | Postoperative pain intensity at rest and at movement measured by an 11-point Numeric Rating Scale (NRS) where 0: no pain and 10: worst imaginary pain) at baseline, at discharge and at day 1, 2, 3, 4, 7, 14, 28 and at 3 months. | at baseline, at discharge and at day 1, 2, 3, 4, 7, 14, 28 and at 3 months after surgery | 
| Simple Shoulder test | Simple shoulder test (SST) measured at baseline and days 7, 14, 28 and 3 months postoperatively. | at baseline and days 7, 14, 28 and 3 months postoperatively. | 
| Adherence | Adherence to study medication on day 1, 2, 3 and 4 postoperatively. Definition compliance: Full compliance: analgesia used as prescribed yes, no compliance: analgesia used as prescribed no | day 1, 2, 3 and 4 postoperatively. | 
| Piritramide | Total amount of intravenous piritramide received in the post-operative care unit (PACU) | after surgery until discharge of PACU (up to 3 hours after surgery) | 
| Rescue medication | The use of rescue medication (Tramadol) at home on day 1, 2, 3 and 4 postoperatively (yes/no) | day 1, 2, 3 and 4 postoperatively | 
| Satisfaction with study medication, surgery and hospital care and telephone follow-up | Satisfaction with study medication, surgery and hospital care and telephone follow-up measured at day 7 and 3 months postoperative measured by an 11-point Numeric Rating Scale (NRS) where 0: totally unsatisfied and 10: totally satisfied | at day 7 and 3 months postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post-operative medication, recovery, ambulant surgery