Clinical Study to Assess Efficacy and Safety of Amiodarone in Treating Patients With Ebola. Virus Disease (EVD) in Sierra Leone. EASE (EMERGENCY Amiodarone Study Against Ebola)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of amiodarone in the treatment of patients afflicted with Ebola virus disease.

Official Title
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Clinical Study to Assess Efficacy and Safety of Amiodarone in Treating Patients With Ebola.

Conditions
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Ebola Virus Disease

Intervention / Treatment
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* Drug: Best Supportive Care
* Drug: Best Supportive Care + Amiodarone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient admitted to the Emergency ETC at Goderich with a clinical diagnosis of Ebola virus disease; patient who consent to participate in the study. Exclusion Criteria: negative RT-PCR tests for Ebola virus age <2 years state of shock upon admission onset of fever for more than 6 days Glasgow Coma Scale <12 known contraindications to administration of amiodarone positive for HIV antibodies.

Ages Eligible for Study
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Minimum Age: 2 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Best Supportive Care<br>Dehydration Ringer's lactate solution or normal saline intravenously Electrolytes should be monitored at regular intervals and corrected as long as vomiting and/or diarrhoea persist Fever intravenous Paracetamol Antimicrobial treatment Prophylactic 5-days course with Ampicillin should be used Pain Paracetamol,Tramadol or Pentazocine Central nervous system disturbances If a patient is restless or confused, prescribe a light sedation utilizing Midazolam, Propofol or Ketamine, preferably in association with Diazepam or Midazolam Seizures Diazepam Vomiting antiemetic medications may provide some relief and facilitate the rehydration Dyspepsia in adults, Omeprazole Diarrhoea in adults, Loperamide Acute bleeding leading to signs of haemorrhagic shock should be treated with whole blood transfusion and supportive care. Patients haemodynamically stable should not be transfused if the Hb level is >7 mg% Septic shock intensive support care Malaria in case of positive initial test, Artesunate | Drug: Best Supportive Care<br>* Dehydration Ringer's lactate solution or normal saline intravenously Electrolytes should be monitored at regular intervals and corrected as long as vomiting and/or diarrhoea persist Fever intravenous Paracetamol Antimicrobial treatment Prophylactic 5-days course with Ampicillin should be used Pain Paracetamol,Tramadol or Pentazocine Central nervous system disturbances If a patient is restless or confused, prescribe a light sedation utilizing Midazolam, Propofol or Ketamine, preferably in association with Diazepam or Midazolam Seizures Diazepam Vomiting antiemetic medications may provide some relief and facilitate the rehydration Dyspepsia in adults, Omeprazole Diarrhoea in adults, Loperamide Acute bleeding leading to signs of haemorrhagic shock should be treated with whole blood transfusion and supportive care. Patients haemodynamically stable should not be transfused if the Hb level is >7 mg% Septic shock intensive support care Malaria in case of positive initial test, Artesunate<br>|
| Experimental: Best Supportive Care + Amiodarone<br>This treatment will be provided to patients in the experimental arm only in addition to best supportive care scheme . During the first 3 days of treatment, the drug must be administered in Glucose 5% solution. Deliver through the largest possible vein inserting a long catheter (if possible a CVP line). Day 1. Dose: 20 mg/kg/die i.v. deliver a loading dose of 5mg/kg in the 1st hour, followed by continuous infusion during the remaining 23 hours. Example: 20 mg /kg of Amiodarone in 500 cc of Glucose 5%. Deliver 125 ml during the 1st hour followed by 16 ml/hour for the remaining 23 hours. Day 2 - Day 3. Dose: 20 mg/kg/die i.v. Continuous infusion over 24 hrs. Example: Glucose 5% 500 ml containing 20 mg/kg of Amiodarone (infusion speed = 21 ml/hour). Day 4 to Day 10. If no significant diarrhea and/or vomiting, shift to oral intake of Amiodarone as follows: Adults: 200 mg tablets, 3 times a day, according to the body weight (30mg/Kg) Children < 29 kg: 5 mg/kg 3 times a day | Drug: Best Supportive Care + Amiodarone<br>* This treatment will be provided to patients in the experimental arm only in addition to best supportive care scheme . During the first 3 days of treatment, the drug must be administered in Glucose 5% solution. Deliver through the largest possible vein inserting a long catheter (if possible a CVP line). Day 1. Dose: 20 mg/kg/die i.v. deliver a loading dose of 5mg/kg in the 1st hour, followed by continuous infusion during the remaining 23 hours. Example: 20 mg /kg of Amiodarone in 500 cc of Glucose 5%. Deliver 125 ml during the 1st hour followed by 16 ml/hour for the remaining 23 hours. Day 2 - Day 3. Dose: 20 mg/kg/die i.v. Continuous infusion over 24 hrs. Example: Glucose 5% 500 ml containing 20 mg/kg of Amiodarone (infusion speed = 21 ml/hour). Day 4 to Day 10. If no significant diarrhea and/or vomiting, shift to oral intake of Amiodarone as follows: Adults: 200 mg tablets, 3 times a day, according to the body weight (30mg/Kg) Children < 29 kg: 5 mg/kg 3 times a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality |  | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | Day 1-10 , 14 | 
| Viral load |  | Day 2, 5, 10 and 14 | 
| Lymphocyte count |  | Day 2, 5, 10 and 14 | 
| IgM anti-Ebola virus antibody titer |  | Day 2, 5, 10 and 14 | 
| IgG anti-Ebola virus antibody titer |  | Day 2, 5, 10 and 14 | 
| Serum concentration of amiodarone |  | Day 2, 5, 10 and 14 | 
| Vital status |  | Day 14 and 30 |