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A Study to Assess the Effect of Ticagrelor in Reducing the Number of Days With Pain in Patients With Sickle Cell Disease (Hestia2)

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: NCT02482298
Recruitment Status : Completed
First Posted : June 26, 2015
Results First Posted : December 14, 2017
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Condition Sickle Cell Disease
Interventions Drug: Ticagrelor
Drug: Placebo
Enrollment 87
Recruitment Details This study was conducted at 26 centers in 8 countries between 09 July 2015 and 16 November 2016.
Pre-assignment Details 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
Arm/Group Title PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Hide Arm/Group Description [Not Specified] 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. [Not Specified]
Period Title: Overall Study
Started 30 27 30
Completed 28 24 27
Not Completed 2 3 3
Reason Not Completed
Withdrawal by Subject             2             1             2
Did Not Fulfill Randomization Criteria             0             1             0
Dev. of Study-Spec. Withdrawal Criteria             0             0             1
Lost to Follow-up             0             1             0
Arm/Group Title PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID Total
Hide Arm/Group Description [Not Specified] 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. [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 30 27 30 87
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 27 participants 30 participants 87 participants
21.6  (3.42) 21.9  (2.72) 23.2  (3.69) 22.2  (3.35)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 27 participants 30 participants 87 participants
Female
16
  53.3%
15
  55.6%
16
  53.3%
47
  54.0%
Male
14
  46.7%
12
  44.4%
14
  46.7%
40
  46.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 27 participants 30 participants 87 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
15
  50.0%
14
  51.9%
17
  56.7%
46
  52.9%
White
15
  50.0%
12
  44.4%
13
  43.3%
40
  46.0%
More than one race
0
   0.0%
1
   3.7%
0
   0.0%
1
   1.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary
Hide Description 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.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP.
Arm/Group Title PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Hide Arm/Group Description:
[Not Specified]
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.
[Not Specified]
Overall Number of Participants Analyzed 30 27 30
Least Squares Mean (90% Confidence Interval)
Unit of Measure: Proportion of days with pain
-0.1802
(-0.2673 to -0.0931)
-0.1352
(-0.2260 to -0.0444)
-0.1001
(-0.1881 to -0.0121)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PLACEBO 10MG BID + PLACEBO 45MG BID, TICAGRELOR 10MG BID + PLACEBO 45MG BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0450
Confidence Interval (2-Sided) 90%
-0.0610 to 0.1510
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.06367
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PLACEBO 10MG BID + PLACEBO 45MG BID, TICAGRELOR 45MG BID + PLACEBO 10MG BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0801
Confidence Interval (2-Sided) 90%
-0.0230 to 0.1832
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.06192
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Average of the Daily Worst Pain Values Reported Via eDiary
Hide Description 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.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP.
Arm/Group Title PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Hide Arm/Group Description:
[Not Specified]
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.
[Not Specified]
Overall Number of Participants Analyzed 30 27 30
Mean (Standard Deviation)
Unit of Measure: Average daily worst pain rating
1.02  (1.106) 1.15  (1.547) 1.74  (2.277)
3.Secondary Outcome
Title Change in Proportion of Days With Analgesic Use Measured by an eDiary
Hide Description To assess the efficacy of 2 different doses of ticagrelor versus placebo in reducing the use of analgesics by patients with sickle cell disease.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP.
Arm/Group Title PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Hide Arm/Group Description:
[Not Specified]
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.
[Not Specified]
Overall Number of Participants Analyzed 30 27 30
Least Squares Mean (90% Confidence Interval)
Unit of Measure: Proportion of days with analgesic use
-0.1991
(-0.2753 to -0.1230)
-0.0799
(-0.1590 to -0.0008)
-0.1016
(-0.1782 to -0.0250)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PLACEBO 10MG BID + PLACEBO 45MG BID, TICAGRELOR 10MG BID + PLACEBO 45MG BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1192
Confidence Interval (2-Sided) 90%
0.0350 to 0.2035
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05059
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PLACEBO 10MG BID + PLACEBO 45MG BID, TICAGRELOR 45MG BID + PLACEBO 10MG BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0975
Confidence Interval (2-Sided) 90%
0.0155 to 0.1795
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04923
Estimation Comments [Not Specified]
4.Other Pre-specified Outcome
Title Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients)
Hide Description To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Hide Arm/Group Description:
[Not Specified]
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.
[Not Specified]
Overall Number of Participants Analyzed 30 26 30
Measure Type: Number
Unit of Measure: Number of patients
Patients with any bleeding events 2 2 2
Pts w/ any bleeding event requiring intervention 2 1 2
5.Other Pre-specified Outcome
Title Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events)
Hide Description To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Hide Arm/Group Description:
[Not Specified]
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.
[Not Specified]
Overall Number of Participants Analyzed 30 26 30
Measure Type: Number
Unit of Measure: Number of events
Total number of bleeding events 2 2 2
Maximum severity of bleeding event: Minor 0 1 0
Max sever. of bleed event: Clin-relevant nonmajor 2 1 2
Maximum severity of bleeding event: Major 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Hide Arm/Group Description [Not Specified] 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. [Not Specified]
All-Cause Mortality
PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/30 (20.00%)      6/26 (23.08%)      5/30 (16.67%)    
Blood and lymphatic system disorders       
Reticulocytopenia † 1  0/30 (0.00%)  0 0/26 (0.00%)  0 1/30 (3.33%)  1
Sickle cell anaemia with crisis † 1  3/30 (10.00%)  7 5/26 (19.23%)  6 3/30 (10.00%)  3
General disorders       
Local swelling † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 0/30 (0.00%)  0
Hepatobiliary disorders       
Hepatic ischaemia † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 0/30 (0.00%)  0
Infections and infestations       
Cellulitis † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 0/30 (0.00%)  0
Gastroenteritis † 1  2/30 (6.67%)  2 0/26 (0.00%)  0 1/30 (3.33%)  1
Lower respiratory tract infection † 1  0/30 (0.00%)  0 1/26 (3.85%)  1 0/30 (0.00%)  0
Injury, poisoning and procedural complications       
Face injury † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 0/30 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  0/30 (0.00%)  0 1/26 (3.85%)  2 0/30 (0.00%)  0
Back pain † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 0/30 (0.00%)  0
Musculoskeletal chest pain † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 0/30 (0.00%)  0
Nervous system disorders       
Headache † 1  0/30 (0.00%)  0 1/26 (3.85%)  1 0/30 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Acute chest syndrome † 1  0/30 (0.00%)  0 1/26 (3.85%)  1 1/30 (3.33%)  1
Vascular disorders       
Vascular occlusion † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 0/30 (0.00%)  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PLACEBO 10MG BID + PLACEBO 45MG BID TICAGRELOR 10MG BID + PLACEBO 45MG BID TICAGRELOR 45MG BID + PLACEBO 10MG BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/30 (53.33%)      15/26 (57.69%)      20/30 (66.67%)    
Blood and lymphatic system disorders       
Sickle cell anaemia with crisis † 1  1/30 (3.33%)  3 1/26 (3.85%)  1 2/30 (6.67%)  3
Gastrointestinal disorders       
Abdominal pain † 1  3/30 (10.00%)  4 5/26 (19.23%)  11 3/30 (10.00%)  3
Nausea † 1  1/30 (3.33%)  1 1/26 (3.85%)  1 3/30 (10.00%)  3
Toothache † 1  1/30 (3.33%)  1 2/26 (7.69%)  2 0/30 (0.00%)  0
Vomiting † 1  1/30 (3.33%)  1 2/26 (7.69%)  3 2/30 (6.67%)  2
General disorders       
Fatigue † 1  2/30 (6.67%)  2 1/26 (3.85%)  1 2/30 (6.67%)  2
Non-cardiac chest pain † 1  3/30 (10.00%)  4 3/26 (11.54%)  10 4/30 (13.33%)  10
Pain † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 2/30 (6.67%)  2
Infections and infestations       
Pneumonia † 1  2/30 (6.67%)  4 2/26 (7.69%)  2 4/30 (13.33%)  4
Upper respiratory tract infection † 1  4/30 (13.33%)  5 1/26 (3.85%)  1 1/30 (3.33%)  1
Urinary tract infection † 1  4/30 (13.33%)  5 2/26 (7.69%)  2 2/30 (6.67%)  2
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  6/30 (20.00%)  23 6/26 (23.08%)  21 9/30 (30.00%)  47
Back pain † 1  7/30 (23.33%)  20 4/26 (15.38%)  10 4/30 (13.33%)  12
Musculoskeletal chest pain † 1  0/30 (0.00%)  0 1/26 (3.85%)  1 2/30 (6.67%)  7
Musculoskeletal pain † 1  2/30 (6.67%)  2 3/26 (11.54%)  5 3/30 (10.00%)  9
Pain in extremity † 1  5/30 (16.67%)  11 4/26 (15.38%)  12 9/30 (30.00%)  22
Nervous system disorders       
Headache † 1  8/30 (26.67%)  23 11/26 (42.31%)  25 8/30 (26.67%)  28
Reproductive system and breast disorders       
Dysmenorrhoea † 1  0/30 (0.00%)  0 1/26 (3.85%)  1 2/30 (6.67%)  4
Respiratory, thoracic and mediastinal disorders       
Cough † 1  0/30 (0.00%)  0 2/26 (7.69%)  2 0/30 (0.00%)  0
Epistaxis † 1  1/30 (3.33%)  1 0/26 (0.00%)  0 2/30 (6.67%)  2
Oropharyngeal pain † 1  2/30 (6.67%)  3 2/26 (7.69%)  3 1/30 (3.33%)  1
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
[Not Specified]
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.
Public disclosure of trial results by Principle Investigators within two years of trial completion requires Sponsor's prior written consent.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Brilinta Global Clinical Leader
Organization: AstraZeneca
Phone: +46 31 776 10 00
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02482298    
Other Study ID Numbers: D5136C00008
First Submitted: June 17, 2015
First Posted: June 26, 2015
Results First Submitted: September 21, 2017
Results First Posted: December 14, 2017
Last Update Posted: December 19, 2018