Trial Outcomes & Findings for A Study to Assess the Effect of Ticagrelor in Reducing the Number of Days With Pain in Patients With Sickle Cell Disease (NCT NCT02482298)
NCT ID: NCT02482298
Last Updated: 2018-12-19
Results Overview
To investigate the efficacy of 2 different doses of ticagrelor versus placebo in reducing the number of days with pain due to sickle cell disease.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
87 participants
Primary outcome timeframe
Baseline through Week 12
Results posted on
2018-12-19
Participant Flow
This study was conducted at 26 centers in 8 countries between 09 July 2015 and 16 November 2016.
The study duration was approximately 18 weeks, consisting of a screening period including a 4-week single-blind placebo treatment for baseline assessments, a 12-week double-blind randomised treatment period, and a 2-week follow-up period. A total of 87 patients were randomized
Participant milestones
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
|
|---|---|---|---|
|
Overall Study
STARTED
|
30
|
27
|
30
|
|
Overall Study
COMPLETED
|
28
|
24
|
27
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
3
|
Reasons for withdrawal
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
2
|
|
Overall Study
Did Not Fulfill Randomization Criteria
|
0
|
1
|
0
|
|
Overall Study
Dev. of Study-Spec. Withdrawal Criteria
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
Baseline Characteristics
A Study to Assess the Effect of Ticagrelor in Reducing the Number of Days With Pain in Patients With Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
n=30 Participants
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
n=27 Participants
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
n=30 Participants
|
Total
n=87 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
21.6 Years
STANDARD_DEVIATION 3.42 • n=5 Participants
|
21.9 Years
STANDARD_DEVIATION 2.72 • n=7 Participants
|
23.2 Years
STANDARD_DEVIATION 3.69 • n=5 Participants
|
22.2 Years
STANDARD_DEVIATION 3.35 • n=4 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
47 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
46 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline through Week 12Population: The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP.
To investigate the efficacy of 2 different doses of ticagrelor versus placebo in reducing the number of days with pain due to sickle cell disease.
Outcome measures
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
n=30 Participants
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
n=27 Participants
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
n=30 Participants
|
|---|---|---|---|
|
Change in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary
|
-0.1802 Proportion of days with pain
90% Confidence Interval 0.05453 • Interval -0.2673 to -0.0931
|
-0.1352 Proportion of days with pain
90% Confidence Interval 0.05287 • Interval -0.226 to -0.0444
|
-0.1001 Proportion of days with pain
90% Confidence Interval 0.05233 • Interval -0.1881 to -0.0121
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP.
To determine the efficacy of 2 different doses of ticagrelor versus placebo in reducing the intensity of pain due to sickle cell disease. Intensity of pain was recorded on an 11-point scale where 0 represented no pain and 10 represented the worst pain imaginable.
Outcome measures
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
n=30 Participants
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
n=27 Participants
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
n=30 Participants
|
|---|---|---|---|
|
Average of the Daily Worst Pain Values Reported Via eDiary
|
1.02 Average daily worst pain rating
Standard Deviation 1.106
|
1.15 Average daily worst pain rating
Standard Deviation 1.547
|
1.74 Average daily worst pain rating
Standard Deviation 2.277
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP.
To assess the efficacy of 2 different doses of ticagrelor versus placebo in reducing the use of analgesics by patients with sickle cell disease.
Outcome measures
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
n=30 Participants
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
n=27 Participants
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
n=30 Participants
|
|---|---|---|---|
|
Change in Proportion of Days With Analgesic Use Measured by an eDiary
|
-0.1991 Proportion of days with analgesic use
90% Confidence Interval 0.08763 • Interval -0.2753 to -0.123
|
-0.0799 Proportion of days with analgesic use
90% Confidence Interval 0.08540 • Interval -0.159 to -0.0008
|
-0.1016 Proportion of days with analgesic use
90% Confidence Interval 0.08664 • Interval -0.1782 to -0.025
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 12Population: The Safety analysis set included all patients who received at least 1 single dose of randomised IP, ticagrelor or placebo, and for whom any post-dose data were available. Patients were analysed according to the actual treatment.
To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD
Outcome measures
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
n=30 Participants
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
n=26 Participants
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
n=30 Participants
|
|---|---|---|---|
|
Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients)
Patients with any bleeding events
|
2 Number of patients
|
2 Number of patients
|
2 Number of patients
|
|
Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients)
Pts w/ any bleeding event requiring intervention
|
2 Number of patients
|
1 Number of patients
|
2 Number of patients
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 12Population: The Safety analysis set included all patients who received at least 1 single dose of randomised IP, ticagrelor or placebo, and for whom any post-dose data were available. Patients were analysed according to the actual treatment.
To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD
Outcome measures
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
n=30 Participants
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
n=26 Participants
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
n=30 Participants
|
|---|---|---|---|
|
Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events)
Total number of bleeding events
|
2 Number of events
|
2 Number of events
|
2 Number of events
|
|
Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events)
Maximum severity of bleeding event: Minor
|
0 Number of events
|
1 Number of events
|
0 Number of events
|
|
Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events)
Max sever. of bleed event: Clin-relevant nonmajor
|
2 Number of events
|
1 Number of events
|
2 Number of events
|
|
Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events)
Maximum severity of bleeding event: Major
|
0 Number of events
|
0 Number of events
|
0 Number of events
|
Adverse Events
PLACEBO 10MG BID + PLACEBO 45MG BID
Serious events: 6 serious events
Other events: 16 other events
Deaths: 0 deaths
TICAGRELOR 10MG BID + PLACEBO 45MG BID
Serious events: 6 serious events
Other events: 15 other events
Deaths: 0 deaths
TICAGRELOR 45MG BID + PLACEBO 10MG BID
Serious events: 5 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
n=30 participants at risk
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
n=26 participants at risk
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
n=30 participants at risk
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Reticulocytopenia
|
0.00%
0/30
|
0.00%
0/26
|
3.3%
1/30 • Number of events 1
|
|
Blood and lymphatic system disorders
Sickle cell anaemia with crisis
|
10.0%
3/30 • Number of events 7
|
19.2%
5/26 • Number of events 6
|
10.0%
3/30 • Number of events 3
|
|
General disorders
Local swelling
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
0.00%
0/30
|
|
Hepatobiliary disorders
Hepatic ischaemia
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
0.00%
0/30
|
|
Infections and infestations
Cellulitis
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
0.00%
0/30
|
|
Infections and infestations
Gastroenteritis
|
6.7%
2/30 • Number of events 2
|
0.00%
0/26
|
3.3%
1/30 • Number of events 1
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/30
|
3.8%
1/26 • Number of events 1
|
0.00%
0/30
|
|
Injury, poisoning and procedural complications
Face injury
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
0.00%
0/30
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/30
|
3.8%
1/26 • Number of events 2
|
0.00%
0/30
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
0.00%
0/30
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
0.00%
0/30
|
|
Nervous system disorders
Headache
|
0.00%
0/30
|
3.8%
1/26 • Number of events 1
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
Acute chest syndrome
|
0.00%
0/30
|
3.8%
1/26 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
|
Vascular disorders
Vascular occlusion
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
0.00%
0/30
|
Other adverse events
| Measure |
PLACEBO 10MG BID + PLACEBO 45MG BID
n=30 participants at risk
|
TICAGRELOR 10MG BID + PLACEBO 45MG BID
n=26 participants at risk
Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments.
|
TICAGRELOR 45MG BID + PLACEBO 10MG BID
n=30 participants at risk
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Sickle cell anaemia with crisis
|
3.3%
1/30 • Number of events 3
|
3.8%
1/26 • Number of events 1
|
6.7%
2/30 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
3/30 • Number of events 4
|
19.2%
5/26 • Number of events 11
|
10.0%
3/30 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
3.3%
1/30 • Number of events 1
|
3.8%
1/26 • Number of events 1
|
10.0%
3/30 • Number of events 3
|
|
Gastrointestinal disorders
Toothache
|
3.3%
1/30 • Number of events 1
|
7.7%
2/26 • Number of events 2
|
0.00%
0/30
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30 • Number of events 1
|
7.7%
2/26 • Number of events 3
|
6.7%
2/30 • Number of events 2
|
|
General disorders
Fatigue
|
6.7%
2/30 • Number of events 2
|
3.8%
1/26 • Number of events 1
|
6.7%
2/30 • Number of events 2
|
|
General disorders
Non-cardiac chest pain
|
10.0%
3/30 • Number of events 4
|
11.5%
3/26 • Number of events 10
|
13.3%
4/30 • Number of events 10
|
|
General disorders
Pain
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
6.7%
2/30 • Number of events 2
|
|
Infections and infestations
Pneumonia
|
6.7%
2/30 • Number of events 4
|
7.7%
2/26 • Number of events 2
|
13.3%
4/30 • Number of events 4
|
|
Infections and infestations
Upper respiratory tract infection
|
13.3%
4/30 • Number of events 5
|
3.8%
1/26 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
13.3%
4/30 • Number of events 5
|
7.7%
2/26 • Number of events 2
|
6.7%
2/30 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.0%
6/30 • Number of events 23
|
23.1%
6/26 • Number of events 21
|
30.0%
9/30 • Number of events 47
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
23.3%
7/30 • Number of events 20
|
15.4%
4/26 • Number of events 10
|
13.3%
4/30 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/30
|
3.8%
1/26 • Number of events 1
|
6.7%
2/30 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.7%
2/30 • Number of events 2
|
11.5%
3/26 • Number of events 5
|
10.0%
3/30 • Number of events 9
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
5/30 • Number of events 11
|
15.4%
4/26 • Number of events 12
|
30.0%
9/30 • Number of events 22
|
|
Nervous system disorders
Headache
|
26.7%
8/30 • Number of events 23
|
42.3%
11/26 • Number of events 25
|
26.7%
8/30 • Number of events 28
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/30
|
3.8%
1/26 • Number of events 1
|
6.7%
2/30 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/30
|
7.7%
2/26 • Number of events 2
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.3%
1/30 • Number of events 1
|
0.00%
0/26
|
6.7%
2/30 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.7%
2/30 • Number of events 3
|
7.7%
2/26 • Number of events 3
|
3.3%
1/30 • Number of events 1
|
Additional Information
Brilinta Global Clinical Leader
AstraZeneca
Phone: +46 31 776 10 00
Results disclosure agreements
- Principal investigator is a sponsor employee Public disclosure of trial results by Principle Investigators within two years of trial completion requires Sponsor's prior written consent.
- Publication restrictions are in place
Restriction type: OTHER