Efficacy and Tolerability of Metamizol in Patients With Episodic Moderate Headache

Study Overview
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Brief Summary
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The objective of the study was to evaluate the efficacy, safety and tolerability of a single peroral dose of 0.5 g and 1.0 g metamizol relative to placebo and 1.0 g acetylsalicylic acid in 2 episodes of moderate tension headache.

Official Title
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A Randomised, Double Blind, Placebo- and Active-controlled Parallel Group Study Investigating the Efficacy and Tolerability of Metamizol 0.5 g and 1.0 g in Patients With Episodic Moderate Tension Headache.

Conditions
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Migraine Disorders

Intervention / Treatment
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* Drug: Metamizol
* Drug: Acetylsalicylic acid (ASA)
* Drug: Metamizol placebo
* Drug: ASA placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between 18 and 65 years old Moderate episodic tension headache according to International Headache Society (I.H.S.) classification 2.1 (2.1.1 and 2.1.2) for at least one year At least two episodes of tension headache per month in the last three months prior to enrolment into this trial The episodes of tension headaches were usually treated by the patient successfully with a non-opioid-analgesic First episodic headache occurred at an age under 50 years Written informed consent according to Good Clinical Practice (GCP) and local regulations The patient was able to fill in the Patient's Diary Exclusion Criteria: The patient usually needs for successful treatment of tension headache Over The Counter (OTC) analgesic in doses exceeding the doses tested here The patient takes an OTC-analgesic normally at the first signs of an episode of tension headache The patient has more than 15 episodes of tension headache per month Female patients whose episodic tension headache is strongly correlated with the start of hormonal contraception Concomitant treatment with (non-) prescriptional analgesics Pre- (less than 4 weeks prior to inclusion in this trial) and/or concomitant treatment with an antidepressive and/or antipsychotic drug Pre- (less than 2 weeks prior to inclusion in this trial) and/or concomitant treatment with any drug such as NSAIDs (Non-Steroidal Anti Inflammatory Drugs), propanolol, metroprolol, flunarizin, cyclandelate, valproic-acid, serotonergic antagonists, ergotamine, dihydroergotamines and benzodiazepines that may influence the headache symptomatology Use of benzodiazepines in the previous 24 hours to the administration of the study drug. Occasional use of benzodiazepines - up to 3 per week - is allowed Use of any drug with analgesic properties in the previous 24 hours to the administration of the study drug Concomitant treatment with any drug containing ASA and/or metamizol Concomitant treatment with anticoagulants such as heparin or coumarin-derivatives Alcohol and drug abuse according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders ) Female patients in child-bearing age not using adequate means of birth control Pregnancy and/or lactation Gastrointestinal ulcers Liver and/or renal disease Bronchial asthma Relevant allergy or known hypersensitivity to the investigational drugs, its excipients and/or to other NSAIDs Participation in another clinical trial within the last 4 weeks and concurrent participation in another clinical trial Patients with active gastroesophageal flux disease (Amendment number 1) Concomitant treatment with analgesics or any other drug that may have influenced the headache symptomatology - including metamizol or ASA -, was referred to its use during the headache episodes under evaluation. As long as appropriate wash-out periods were respected, analgesics were allowed in between the episodes of tension headache (TH) and their use as a rescue medication did not lead to the exclusion of the patient (Amendment number 2)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metamizol high & Placebo<br> | Drug: Metamizol<br> <br> Drug: Metamizol placebo<br> <br> |
| Experimental: Metamizol low & Placebo<br> | Drug: Metamizol<br> <br> Drug: Metamizol placebo<br> <br> |
| Active Comparator: Acetylsalicylic acid & Placebo<br> | Drug: Acetylsalicylic acid (ASA)<br> <br> Drug: ASA placebo<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Metamizol placebo<br> <br> Drug: ASA placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-interval weighted sum of pain intensity difference (SPID) on a Visual Analogue Scale (VAS) |  | before and 30 minutes, 1, 2, 3, and 4 hours after drug intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity difference (PID) on a VAS |  | before and 30 minutes, 1, 2, 3, and 4 hours after drug intake | 
| Maximum pain intensity difference (MAXPID) on a VAS |  | before and 30 minutes, 1, 2, 3, and 4 hours after drug intake | 
| Number of patients with at least a 50% pain reduction on a VAS |  | before and 30 minutes, 1, 2, 3, and 4 hours after drug intake | 
| Time to 50% pain intensity reduction on a VAS |  | before and 30 minutes, 1, 2, 3, and 4 hours after drug intake | 
| Maximum pain relief (MAXPAR) on a Verbal Rating Scale (VRS) |  | 30 minutes, 1, 2, 3, and 4 hours after drug intake | 
| Total pain relief (TOTPAR) on a VRS |  | 30 minutes, 1, 2, 3, and 4 hours after drug intake | 
| Number of patients using rescue medication |  | 2, 3, and 4 hours after drug intake | 
| Global efficacy assessment on a VRS by the patient and investigator |  | 4 hours after drug intake | 
| Number of patients with adverse events |  | up to 2 months |