Multiple Treatments for Ebola Virus Disease (EVD)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether multiple therapeutic regimens are effective in the treatment of Ebola Virus Disease (EVD)

Detailed Description
-----------------
The ongoing epidemic of EVD has ravaged parts of West Africa, with initial cases reported in December 2013. There is no licensed specific therapy for the disease, which has a case-fatality rate of approximately 50-70%. Although anecdotal clinical data, recent studies in animal models, and in vitro screening suggest that treatment of EVD patients with anti-viral agents, immune modifying agents, and/or convalescent blood products may be effective, they have not been evaluated in clinical trials. This multi-arm clinical trial will evaluate the efficacy and safety of multiple regimens, both as mono-therapy and combination therapy. Provision of these regimens, if found effective and safe, would have a major impact on the current and future epidemics by providing effective treatment options. As described for previous adaptive trials, a randomization probability for each of the treatment regimens is created based on 14-day mortality, and is used for weighting randomization of subsequently enrolled participants. Participants will continually be preferentially assigned to regimens with better initial performance. New agents can be added or existing agents removed as the trial evolves.

Official Title
-----------------
An Adaptive Randomized Trial Comparing Multiple Treatments for Ebola Virus (EBOV) Infected Children and Adults

Conditions
-----------------
Ebola Virus Disease

Intervention / Treatment
-----------------
* Drug: Azithromycin
* Drug: Sunitinib and Erlotinib
* Drug: Atorvastatin and Irbesartan
* Other: IV fluids and laboratory testing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females aged 6 months and >8kg in weight Confirmed case of EVD Admission to the hospital < 48 hours prior to enrollment Participant or family member/guardian able and willing to provide signed informed consent Exclusion Criteria: Prior treatment with any other specific experimental anti-EVD product, or expectation to receive another experimental anti-EVD product during the course of the study (this does not include general supportive care or nutritional supplements routinely administered to all hospitalized patients with EVD) Unresponsive In the treating physicians opinion, an inability to comply with the study treatment regimen

Ages Eligible for Study
-----------------
Minimum Age: 6 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azithromycin<br>Azithromycin, IV fluids and laboratory testing | Drug: Azithromycin<br>* Adults (>18 yrs): 3 x 500mg tablets daily for 5 days; Children (6 months to <18 yrs): 30mg/kg (oral suspension) daily for 5 days<br>* Other names: Zithromax;Other: IV fluids and laboratory testing<br>* All arms will receive aggressive IV fluid rehydration and frequent laboratory tests to assist with medical management as indicated.<br>|
| Experimental: Sunitinib and Erlotinib<br>Sunitinib, Erlotinib, IV fluids and laboratory testing | Drug: Sunitinib and Erlotinib<br>* Sunitinib - Adults (>18 yrs): 1 x 50mg tablet daily for 7 days; Children (6 months to <18 yrs): 0.83 mg/kg (oral suspension) daily for 7 days. Erlotinib - Adults (>18 yrs): 1 x 150mg tablet daily for 7 days; Children (8kg to <20kg): 3.5 mg/kg daily for 7 days; Children (>20kg to <30kg): 3.0 mg/kg daily for 7 days; Children (>30kg to < 18 yrs): 25 mg/kg daily for 7 days<br>* Other names: Tarceva;Other: IV fluids and laboratory testing<br>* All arms will receive aggressive IV fluid rehydration and frequent laboratory tests to assist with medical management as indicated.<br>|
| Experimental: Atorvastatin and Irbesartan<br>Atorvastatin, Irbesartan, IV fluids and laboratory testing | Drug: Atorvastatin and Irbesartan<br>* Atorvastatin - Adults (>18 yrs): 1 x 40mg tablet daily until discharge; Children (6 years to <18 yrs): 1 x 40mg tablet daily until discharge; Irbesartan - Adults (>18 yrs): 1 x 150mg tablets daily until discharge; Children (6 years to <18 yrs): 1 x 75mg tablet daily until discharge.<br>* Other names: Avapro;Other: IV fluids and laboratory testing<br>* All arms will receive aggressive IV fluid rehydration and frequent laboratory tests to assist with medical management as indicated.<br>|
| Other: IV fluids and laboratory testing<br>no additional treatment | Other: IV fluids and laboratory testing<br>* All arms will receive aggressive IV fluid rehydration and frequent laboratory tests to assist with medical management as indicated.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death by 14 days |  | 14 days after starting treatment regimen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in viral load |  | 14 days after starting treatment regimen | 
| 2-week post discharge clinical sequelae, including signs and symptoms and laboratory abnormalities |  | 14 days after starting treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
EVD, Ebola, Adaptive design, therapeutics