Trial Outcomes & Findings for Emergency Evaluation of Convalescent Plasma for Ebola Viral Disease (EVD) in Guinea (NCT NCT02342171)
NCT ID: NCT02342171
Last Updated: 2019-07-22
Results Overview
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
COMPLETED
PHASE2/PHASE3
606 participants
14 days
2019-07-22
Participant Flow
Participant milestones
| Measure |
Convalescent Plasma
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Overall Study
STARTED
|
99
|
507
|
|
Overall Study
COMPLETED
|
84
|
418
|
|
Overall Study
NOT COMPLETED
|
15
|
89
|
Reasons for withdrawal
| Measure |
Convalescent Plasma
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Overall Study
Death
|
4
|
87
|
|
Overall Study
Received favipiravir
|
10
|
0
|
|
Overall Study
Missing cycle treshold value
|
1
|
0
|
|
Overall Study
Unknown outcome
|
0
|
1
|
|
Overall Study
Missing age data
|
0
|
1
|
Baseline Characteristics
Only including patients with any symptom at baseline
Baseline characteristics by cohort
| Measure |
Convalescent Plasma
n=84 Participants
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.
|
Standard Care
n=418 Participants
The control arm will consist of historical controls having being treated with standard of care
|
Total
n=502 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
29 years
n=84 Participants
|
28 years
n=418 Participants
|
28 years
n=502 Participants
|
|
Age, Customized
Age · <5 years
|
5 Participants
n=84 Participants
|
23 Participants
n=418 Participants
|
28 Participants
n=502 Participants
|
|
Age, Customized
Age · 5-15 years
|
8 Participants
n=84 Participants
|
53 Participants
n=418 Participants
|
61 Participants
n=502 Participants
|
|
Age, Customized
Age · 16-44 years
|
56 Participants
n=84 Participants
|
258 Participants
n=418 Participants
|
314 Participants
n=502 Participants
|
|
Age, Customized
Age · >45 years
|
15 Participants
n=84 Participants
|
84 Participants
n=418 Participants
|
99 Participants
n=502 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=84 Participants
|
210 Participants
n=418 Participants
|
258 Participants
n=502 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=84 Participants
|
208 Participants
n=418 Participants
|
244 Participants
n=502 Participants
|
|
Cycle-threshold on PCR
|
27.3 Number of cycles
n=84 Participants
|
26.0 Number of cycles
n=418 Participants
|
26.3 Number of cycles
n=502 Participants
|
|
Number of participants per PCR Cycle-threshold interval
<25 cycles
|
21 Participants
n=84 Participants
|
159 Participants
n=418 Participants
|
180 Participants
n=502 Participants
|
|
Number of participants per PCR Cycle-threshold interval
25.0-29.9 cycles
|
41 Participants
n=84 Participants
|
183 Participants
n=418 Participants
|
224 Participants
n=502 Participants
|
|
Number of participants per PCR Cycle-threshold interval
>29.9 cycles
|
22 Participants
n=84 Participants
|
76 Participants
n=418 Participants
|
98 Participants
n=502 Participants
|
|
Nausea and vomiting
|
42 Participants
n=84 Participants
|
203 Participants
n=418 Participants
|
245 Participants
n=502 Participants
|
|
Diarrhea
|
29 Participants
n=84 Participants
|
155 Participants
n=418 Participants
|
184 Participants
n=502 Participants
|
|
Weakness or asthenia
|
77 Participants
n=84 Participants
|
353 Participants
n=418 Participants
|
430 Participants
n=502 Participants
|
|
Pain
|
73 Participants
n=84 Participants
|
342 Participants
n=418 Participants
|
415 Participants
n=502 Participants
|
|
Cough
|
11 Participants
n=84 Participants
|
40 Participants
n=418 Participants
|
51 Participants
n=502 Participants
|
|
Difficulty breathing
|
4 Participants
n=84 Participants
|
11 Participants
n=418 Participants
|
15 Participants
n=502 Participants
|
|
Difficulty swallowing
|
15 Participants
n=84 Participants
|
39 Participants
n=418 Participants
|
54 Participants
n=502 Participants
|
|
Hiccups
|
7 Participants
n=84 Participants
|
38 Participants
n=418 Participants
|
45 Participants
n=502 Participants
|
|
Eye redness
|
34 Participants
n=84 Participants
|
83 Participants
n=418 Participants
|
117 Participants
n=502 Participants
|
|
Unusual bleeding
|
5 Participants
n=84 Participants
|
21 Participants
n=418 Participants
|
26 Participants
n=502 Participants
|
|
Disorientation or agitation
|
0 Participants
n=84 Participants
|
2 Participants
n=418 Participants
|
2 Participants
n=502 Participants
|
|
Anuria
|
1 Participants
n=84 Participants
|
1 Participants
n=418 Participants
|
2 Participants
n=502 Participants
|
|
Seizures
|
0 Participants
n=84 Participants
|
1 Participants
n=418 Participants
|
1 Participants
n=502 Participants
|
|
Duration of symptoms >6 days
|
14 Participants
n=73 Participants • Only including patients with any symptom at baseline
|
203 Participants
n=412 Participants • Only including patients with any symptom at baseline
|
217 Participants
n=485 Participants • Only including patients with any symptom at baseline
|
|
Coexisting chronic medical condition
Infectious
|
1 Participants
n=84 Participants
|
2 Participants
n=418 Participants
|
3 Participants
n=502 Participants
|
|
Coexisting chronic medical condition
Noninfectious
|
1 Participants
n=84 Participants
|
3 Participants
n=418 Participants
|
4 Participants
n=502 Participants
|
PRIMARY outcome
Timeframe: 14 daysEffect 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
Outcome measures
| Measure |
Convalescent Plasma
n=84 Participants
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.
|
Standard Care
n=418 Participants
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Survival at Day 14 After Start of Intervention
|
58 Participants
|
260 Participants
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Outcome was only measured in the intervention group. Data (historical) not available for "Standard care" group.
Effect of convalescent plasma in improving patients survival at day 30
Outcome measures
| Measure |
Convalescent Plasma
n=84 Participants
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Number of Participants With 30 Days Survival
|
57 Participants
|
—
|
SECONDARY outcome
Timeframe: 30 daysPopulation: 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.
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).
Outcome measures
| Measure |
Convalescent Plasma
n=71 Participants
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Titer of Ebola Viral RNA
Lowest dose (antibody range 176.4 - 511.9)
|
1 Cycles
Interval 1.0 to 1.0
|
—
|
|
Titer of Ebola Viral RNA
Middle dose (antibody range 513.3 - 740.6)
|
3.24 Cycles
Interval 0.87 to 5.61
|
—
|
|
Titer of Ebola Viral RNA
Highest dose (antibody range 747.9 - 1628.7)
|
2.34 Cycles
Interval -0.09 to 4.78
|
—
|
SECONDARY outcome
Timeframe: 30 daysPopulation: 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.
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).
Outcome measures
| Measure |
Convalescent Plasma
n=71 Participants
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Titer of Ebola Viral RNA
Lowest dose ((antibody range 176.4 - 511.9)
|
1 Cycles
Interval 1.0 to 1.0
|
—
|
|
Titer of Ebola Viral RNA
Middle dose (antibody range 513.3 - 740.6)
|
0.30 Cycles
Interval -2.3 to 2.9
|
—
|
|
Titer of Ebola Viral RNA
Highest dose (antibody range 747.9 - 1628.7)
|
-0.46 Cycles
Interval -2.99 to 2.08
|
—
|
SECONDARY outcome
Timeframe: 14 daysPopulation: 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.
To assess the relationship between EVD antibody levels (anti-EBOV IgG) and death in patients who received Convalescent Plasma
Outcome measures
| Measure |
Convalescent Plasma
n=71 Participants
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Number of Participants Who Died Corresponding to EV Antibody Levels (Anti-EBOV IgG)
Low (antibody range 176.4 - 511.9)
|
5 Participants
|
—
|
|
Number of Participants Who Died Corresponding to EV Antibody Levels (Anti-EBOV IgG)
Medium (antibody range 513.3 - 740.6)
|
11 Participants
|
—
|
|
Number of Participants Who Died Corresponding to EV Antibody Levels (Anti-EBOV IgG)
High (antibody range 747.9 - 1628.7)
|
8 Participants
|
—
|
SECONDARY outcome
Timeframe: 14 daysPopulation: 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.
To assess the relationship between EVD antibody levels (neutralizing antibodies) and death in patients who received CP
Outcome measures
| Measure |
Convalescent Plasma
n=71 Participants
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Number of Participants Who Died Corresponding to EV Antibody Levels (Neutralizing Antibodies)
Low(antibody range 176.4 - 511.9)
|
6 Participants
|
—
|
|
Number of Participants Who Died Corresponding to EV Antibody Levels (Neutralizing Antibodies)
Medium (antibody range 513.3 - 740.6)
|
8 Participants
|
—
|
|
Number of Participants Who Died Corresponding to EV Antibody Levels (Neutralizing Antibodies)
High (antibody range 747.9 - 1628.7)
|
10 Participants
|
—
|
SECONDARY outcome
Timeframe: 30 daysTo assess the occurrence of serious adverse reactions (SARs) related to CP transfusion in Ebola patients
Outcome measures
| Measure |
Convalescent Plasma
n=99 Participants
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Number of Transfusion-related Serious Adverse Reactions (SARs)
|
0 SARs
|
—
|
SECONDARY outcome
Timeframe: 9 monthsPopulation: Overall Number of Participants Analyzed refers to health workers administering CP; not to the participants receiving CP.
To assess the occurrence of safety risks related to CP transfusion in health workers administering the treatments. This will be observed throughout the study
Outcome measures
| Measure |
Convalescent Plasma
n=12 Participants
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.
|
Standard Care
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Number of Professional Safety Incidents
|
0 Professional safety incidents
|
—
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Pre-specified sub-group comparison
To determine Ct as risk factor for mortality despite administration of CP.
Outcome measures
| Measure |
Convalescent Plasma
n=84 Participants
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.
|
Standard Care
n=418 Participants
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Mortality Risk Factor: Ct
10-24.9 cycles
|
11 Participants
|
90 Participants
|
|
Mortality Risk Factor: Ct
25-29.9 cycles
|
11 Participants
|
56 Participants
|
|
Mortality Risk Factor: Ct
30-39.9 cycles
|
4 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Pre-specified sub-group comparison
To determine age as risk factor for mortality despite administration of CP.
Outcome measures
| Measure |
Convalescent Plasma
n=84 Participants
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.
|
Standard Care
n=418 Participants
The control arm will consist of historical controls having being treated with standard of care
|
|---|---|---|
|
Mortality Risk Factor: Age
<5 years old
|
1 Participants
|
15 Participants
|
|
Mortality Risk Factor: Age
5-15 years old
|
1 Participants
|
10 Participants
|
|
Mortality Risk Factor: Age
16-44 years old
|
16 Participants
|
90 Participants
|
|
Mortality Risk Factor: Age
>45 years old
|
8 Participants
|
43 Participants
|
Adverse Events
Convalescent Plasma
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Convalescent Plasma
n=84 participants at risk
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.
|
|---|---|
|
General disorders
Increase in temperature
|
6.0%
5/84 • 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.
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.
|
|
Skin and subcutaneous tissue disorders
Itching or skin rash
|
4.8%
4/84 • 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.
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.
|
|
General disorders
Nausea
|
1.2%
1/84 • 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.
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.
|
Additional Information
Prof. Dr. Johan van Griensven
Institute of Tropical Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place