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Emergency Evaluation of Convalescent Plasma for Ebola Viral Disease (EVD) in Guinea (Ebola-Tx)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02342171
Recruitment Status : Completed
First Posted : January 19, 2015
Results First Posted : July 1, 2019
Last Update Posted : July 22, 2019
Sponsor:
Collaborators:
National Blood Transfusion Centre (NBTC), Conakry, Guinea
Gamal Abdel Nasser University of Conakry
National Center for Training and Research of Maferinyah, Guinea
Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
University of Oxford
University of Liverpool
London School of Hygiene and Tropical Medicine
Aix Marseille Université
UBIVE, Institut Pasteur, Paris, France
Institut National de la Santé Et de la Recherche Médicale, France
Etablissement Français du Sang
Belgian Red Cross
Institut Pasteur, Dakar, Sénégal
Médecins Sans Frontières, Belgium
World Health Organization
International Severe Acute Respiratory and Emerging Infection Consortium
Information provided by (Responsible Party):
Institute of Tropical Medicine, Belgium

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemorrhagic Fever, Ebola
Intervention Other: Convalescent Plasma
Enrollment 606
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Convalescent Plasma Standard Care
Hide Arm/Group Description

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

The control arm will consist of historical controls having being treated with standard of care
Period Title: Overall Study
Started 99 507
Completed 84 418
Not Completed 15 89
Reason Not Completed
Death             4             87
Received favipiravir             10             0
Missing cycle treshold value             1             0
Unknown outcome             0             1
Missing age data             0             1
Arm/Group Title Convalescent Plasma Standard Care Total
Hide Arm/Group Description

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

The control arm will consist of historical controls having being treated with standard of care Total of all reporting groups
Overall Number of Baseline Participants 84 418 502
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 84 participants 418 participants 502 participants
29
(0 to 75)
28
(0 to 87)
28
(0 to 87)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Age Number Analyzed 84 participants 418 participants 502 participants
<5 years 5 23 28
5-15 years 8 53 61
16-44 years 56 258 314
>45 years 15 84 99
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
Female
48
  57.1%
210
  50.2%
258
  51.4%
Male
36
  42.9%
208
  49.8%
244
  48.6%
Cycle-threshold on PCR   [1] 
Median (Full Range)
Unit of measure:  Number of cycles
Number Analyzed 84 participants 418 participants 502 participants
27.3
(19.2 to 35.8)
26.0
(15.2 to 39.4)
26.3
(15.2 to 39.4)
[1]
Measure Description: The value represents the number of cycles the PCR has run before reaching a threshold value of a positive result.
Number of participants per PCR Cycle-threshold interval   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
<25 cycles
21
  25.0%
159
  38.0%
180
  35.9%
25.0-29.9 cycles
41
  48.8%
183
  43.8%
224
  44.6%
>29.9 cycles
22
  26.2%
76
  18.2%
98
  19.5%
[1]
Measure Description: The value represents the number of cycles the PCR has run before reaching a threshold value of a positive result.
Nausea and vomiting  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
42
  50.0%
203
  48.6%
245
  48.8%
Diarrhea  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
29
  34.5%
155
  37.1%
184
  36.7%
Weakness or asthenia  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
77
  91.7%
353
  84.4%
430
  85.7%
Pain  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
73
  86.9%
342
  81.8%
415
  82.7%
Cough  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
11
  13.1%
40
   9.6%
51
  10.2%
Difficulty breathing  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
4
   4.8%
11
   2.6%
15
   3.0%
Difficulty swallowing  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
15
  17.9%
39
   9.3%
54
  10.8%
Hiccups  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
7
   8.3%
38
   9.1%
45
   9.0%
Eye redness   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
34
  40.5%
83
  19.9%
117
  23.3%
[1]
Measure Description: Includes both conjunctivitis and conjunctival bleeding
Unusual bleeding   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
5
   6.0%
21
   5.0%
26
   5.2%
[1]
Measure Description: Excluding conjunctival bleeding
Disorientation or agitation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
0
   0.0%
2
   0.5%
2
   0.4%
Anuria  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
1
   1.2%
1
   0.2%
2
   0.4%
Seizures  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 418 participants 502 participants
0
   0.0%
1
   0.2%
1
   0.2%
Duration of symptoms >6 days   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 412 participants 485 participants
14
  19.2%
203
  49.3%
217
  44.7%
[1]
Measure Analysis Population Description: Only including patients with any symptom at baseline
Coexisting chronic medical condition  
Measure Type: Count of Participants
Unit of measure:  Participants
Infectious Number Analyzed 84 participants 418 participants 502 participants
1
   1.2%
2
   0.5%
3
   0.6%
Noninfectious Number Analyzed 84 participants 418 participants 502 participants
1
   1.2%
3
   0.7%
4
   0.8%
1.Primary Outcome
Title Survival at Day 14 After Start of Intervention
Hide Description Effect of convalescent plasma in improving patients survival at day 14; it will be considered clinically significant if there is an absolute decrease in the case fatality rate of 20% or more, compared to SC alone
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Convalescent Plasma Standard Care
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

The control arm will consist of historical controls having being treated with standard of care
Overall Number of Participants Analyzed 84 418
Measure Type: Count of Participants
Unit of Measure: Participants
58
  69.0%
260
  62.2%
2.Secondary Outcome
Title Number of Participants With 30 Days Survival
Hide Description Effect of convalescent plasma in improving patients survival at day 30
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome was only measured in the intervention group. Data (historical) not available for "Standard care" group.
Arm/Group Title Convalescent Plasma
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

Overall Number of Participants Analyzed 84
Measure Type: Count of Participants
Unit of Measure: Participants
57
  67.9%
3.Secondary Outcome
Title Titer of Ebola Viral RNA
Hide Description

To assess the relationship between EVD antibody levels (EBOV IgG) in donated plasma and the changes in levels of viral RNA in patients who received Convalescent Plasma.

The outcome shows the overall association between antibody dose category and change in Cycle threshold (Ct) value pre and post transfusion (Ct is the number of cycles that have to be run before reaching a threshold value of a positive result).

Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description

Total dose for antibody levels was categorized in three equal-sized groups (tertiles), with the lowest dose category as reference.

71 out of 84 participants were defined as the analysis population. Children (<16 years) were excluded from the analysis as dosing of CP was done according to body weight, which was not recorded for many adult patients.

Arm/Group Title Convalescent Plasma
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

Overall Number of Participants Analyzed 71
Mean (95% Confidence Interval)
Unit of Measure: Cycles
Lowest dose (antibody range 176.4 - 511.9) Number Analyzed 24 participants
1
(1 to 1)
Middle dose (antibody range 513.3 - 740.6) Number Analyzed 24 participants
3.24
(0.87 to 5.61)
Highest dose (antibody range 747.9 - 1628.7) Number Analyzed 23 participants
2.34
(-0.09 to 4.78)
4.Secondary Outcome
Title Titer of Ebola Viral RNA
Hide Description

To assess the relationship between EVD antibody levels (neutralizing antibodies) in donated plasma and the changes in levels of viral RNA in patients who received Convalescent Plasma.

The outcome shows the overall association between antibody dose category and change in Cycle threshold (Ct) value pre and post transfusion (Ct is the number of cycles that have to be run before reaching a threshold value of a positive result).

Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description

Total dose for antibody levels was categorized in three equal-sized groups (tertiles), with the lowest dose category as reference.

71 out of 84 participants were defined as the analysis population. Children (<16 years) were excluded from the analysis as dosing of CP was done according to body weight, which was not recorded for many adult patients.

Arm/Group Title Convalescent Plasma
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

Overall Number of Participants Analyzed 71
Mean (95% Confidence Interval)
Unit of Measure: Cycles
Lowest dose ((antibody range 176.4 - 511.9) Number Analyzed 24 participants
1
(1 to 1)
Middle dose (antibody range 513.3 - 740.6) Number Analyzed 24 participants
0.30
(-2.30 to 2.90)
Highest dose (antibody range 747.9 - 1628.7) Number Analyzed 23 participants
-0.46
(-2.99 to 2.08)
5.Secondary Outcome
Title Number of Participants Who Died Corresponding to EV Antibody Levels (Anti-EBOV IgG)
Hide Description To assess the relationship between EVD antibody levels (anti-EBOV IgG) and death in patients who received Convalescent Plasma
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
Overall Number of Participants Analyzed divided in 3 equal groups depending on total dose of antibodies. 71 out of 84 participants were defined as the analysis population. Children (<16 years) were excluded from analysis as dosing of CP was done according to body weight, which was not recorded for many adult patients.
Arm/Group Title Convalescent Plasma
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

Overall Number of Participants Analyzed 71
Measure Type: Count of Participants
Unit of Measure: Participants
Low (antibody range 176.4 - 511.9) Number Analyzed 24 participants
5
  20.8%
Medium (antibody range 513.3 - 740.6) Number Analyzed 24 participants
11
  45.8%
High (antibody range 747.9 - 1628.7) Number Analyzed 23 participants
8
  34.8%
6.Secondary Outcome
Title Number of Participants Who Died Corresponding to EV Antibody Levels (Neutralizing Antibodies)
Hide Description To assess the relationship between EVD antibody levels (neutralizing antibodies) and death in patients who received CP
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
Overall Number of Participants Analyzed divided in 3 equal groups depending on total dose of antibodies. Children (<16 years) were excluded from analysis as dosing of CP was done according to body weight, which was not recorded for many adult patients.
Arm/Group Title Convalescent Plasma
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

Overall Number of Participants Analyzed 71
Measure Type: Count of Participants
Unit of Measure: Participants
Low(antibody range 176.4 - 511.9) Number Analyzed 24 participants
6
  25.0%
Medium (antibody range 513.3 - 740.6) Number Analyzed 24 participants
8
  33.3%
High (antibody range 747.9 - 1628.7) Number Analyzed 23 participants
10
  43.5%
7.Secondary Outcome
Title Number of Transfusion-related Serious Adverse Reactions (SARs)
Hide Description To assess the occurrence of serious adverse reactions (SARs) related to CP transfusion in Ebola patients
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Convalescent Plasma
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

Overall Number of Participants Analyzed 99
Measure Type: Number
Unit of Measure: SARs
0
8.Secondary Outcome
Title Number of Professional Safety Incidents
Hide Description To assess the occurrence of safety risks related to CP transfusion in health workers administering the treatments. This will be observed throughout the study
Time Frame 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
Overall Number of Participants Analyzed refers to health workers administering CP; not to the participants receiving CP.
Arm/Group Title Convalescent Plasma
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: Professional safety incidents
0
9.Secondary Outcome
Title Mortality Risk Factor: Ct
Hide Description To determine Ct as risk factor for mortality despite administration of CP.
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Pre-specified sub-group comparison
Arm/Group Title Convalescent Plasma Standard Care
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

The control arm will consist of historical controls having being treated with standard of care
Overall Number of Participants Analyzed 84 418
Measure Type: Count of Participants
Unit of Measure: Participants
10-24.9 cycles Number Analyzed 21 participants 159 participants
11
  52.4%
90
  56.6%
25-29.9 cycles Number Analyzed 41 participants 183 participants
11
  26.8%
56
  30.6%
30-39.9 cycles Number Analyzed 22 participants 76 participants
4
  18.2%
12
  15.8%
10.Secondary Outcome
Title Mortality Risk Factor: Age
Hide Description To determine age as risk factor for mortality despite administration of CP.
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Pre-specified sub-group comparison
Arm/Group Title Convalescent Plasma Standard Care
Hide Arm/Group Description:

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

The control arm will consist of historical controls having being treated with standard of care
Overall Number of Participants Analyzed 84 418
Measure Type: Count of Participants
Unit of Measure: Participants
<5 years old Number Analyzed 5 participants 23 participants
1
  20.0%
15
  65.2%
5-15 years old Number Analyzed 8 participants 53 participants
1
  12.5%
10
  18.9%
16-44 years old Number Analyzed 56 participants 258 participants
16
  28.6%
90
  34.9%
>45 years old Number Analyzed 15 participants 84 participants
8
  53.3%
43
  51.2%
Time Frame All adverse events related to the intervention up to 4 hours after completion of the transfusion. All deaths possibly related to the intervention up to 14 days after completion of the transfusion.
Adverse Event Reporting Description

Due to the nature of the symptoms of EVD (high mortality rate, hospital admissions, disability and life-threatening conditions), the investigation of safety and tolerability of the intervention will focus on Adverse Reactions.

An Adverse Reaction is any untoward and unintended response in a participant to the study treatment, which is related (or has a reasonable possibility of being related) to any dose of the investigational product administered to that participant.

 
Arm/Group Title Convalescent Plasma
Hide Arm/Group Description

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children <45kg

Convalescent Plasma: Patients will be treated with plasma from recovered EVD patients.

No data from "standard care" group available as this is based on historical data.

All-Cause Mortality
Convalescent Plasma
Affected / at Risk (%)
Total   26/84 (30.95%) 
Hide Serious Adverse Events
Convalescent Plasma
Affected / at Risk (%)
Total   0/84 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Convalescent Plasma
Affected / at Risk (%)
Total   8/84 (9.52%) 
General disorders   
Increase in temperature *  5/84 (5.95%) 
Nausea *  1/84 (1.19%) 
Skin and subcutaneous tissue disorders   
Itching or skin rash *  4/84 (4.76%) 
*
Indicates events were collected by non-systematic assessment
There are clear limitations with respect to the use of a historical control group, and we cannot exclude the possibility that unmeasured confounding factors may have biased the mortality comparison.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof. Dr. Johan van Griensven
Organization: Institute of Tropical Medicine
Phone: +3232476426
EMail: jvangriensven@itg.be
Layout table for additonal information
Responsible Party: Institute of Tropical Medicine, Belgium
ClinicalTrials.gov Identifier: NCT02342171    
Other Study ID Numbers: ITM0614
First Submitted: January 12, 2015
First Posted: January 19, 2015
Results First Submitted: December 14, 2017
Results First Posted: July 1, 2019
Last Update Posted: July 22, 2019