CompletedNCT02482298Hestia2Updated Dec 19, 2018Results posted

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

A Phase 2 interventional study of Ticagrelor and Placebo in Sickle Cell Disease, sponsored by AstraZeneca. Completed at 20 sites in 8 countries. Open to participants aged 18 Years to 30 Years. Per ClinicalTrials.gov, last updated 2018-12-19.

Sponsored by AstraZeneca · Phase 2, Interventional, and Prevention

Phase: Phase 2
Study type: Interventional
Enrollment: 87
Allocation: Randomized
Ages: 18 Years to 30 Years
Sex: All

Study summary

The purpose of this study is to determine whether ticagrelor is effective in reducing the number of days of pain, intensity of pain, and reducing the use of analgesics due to sickle cell disease

Read the detailed description

This is a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, study evaluating 2 doses of ticagrelor in 90 patients aged 18 to 30 years, with sickle cell disease (SCD). Patients will be randomised to double-blind double-dummy treatment period in a 1:1:1 ratio (30 to each treatment group) to receive ticagrelor 10 mg twice daily (bid), or ticagrelor 45 mg bid, or placebo bid to determine the frequency of days with pain using an electronic diary (eDiary) every day. Approximately 180 patients will be enrolled. Patient will be followed for safety assessment during and after 2 weeks of treatment completion.

During the 16 week treatment period, patients will complete a daily eDiary concerning daily pain intensity, pain location, use of analgesics and absence from school or work. At the end of the study patients will be asked to rate the change in their sickle cell pain compared to the start of treatment. Platelet aggregation will be measured and reported as P2Y12 reaction units (PRU) pre-dose and 2 hours post-dose at week 4 and week 5 after treatment start. Pharmacokinetic (PK) parameters will be measured at 2 hours post-dose at week 4, and pre-dose and at 2 hours post-dose at week 5. Biomarkers will be assessed pre-dose at week 4, week 5 and week 8. During the study, patients will be evaluated for adverse events (AEs) including bleeding and vaso-occlusive crisis (VOC).

Conditions studied

Sickle Cell Disease

Browse trials for

Anemia, Sickle Cell 1,103

Keywords

Sickle cell disease
Young adults
Hestia2
Ticagrelor

In context

Anemia, Sickle Cell

1,103 studies on the registry are indexed under Anemia, Sickle Cell; 235 are open to participants now.

This study's enrollment of 87 is above the median of 40 across 750 interventional studies indexed under Anemia, Sickle Cell.

Browse Anemia, Sickle Cell studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 30 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Confirmed medical history or diagnosis of homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β0) by HPLC
If treated with hydroxyurea, the dose must have been stable for 3 months

Exclusion criteria

Exclusion Criteria:

History of transient ischaemic attack or clinically overt cerebrovascular accident
Moderate or severe hepatic impairment
Treatment with chronic red blood cell transfusion therapy
Pre-dominate cause of pain is not sickle cell disease related
Chronic treatment with anticoagulants or antiplatelet drugs.

Study design

Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 87 participants (actual)

Study arms

Experimental
Dose A
Drug: Ticagrelor
Experimental
Dose B
Drug: Ticagrelor
Placebo comparator
Placebo
Drug: Placebo

Interventions

DrugTicagrelor
Two arms: 1) 10 mg ticagrelor + 45 mg ticagrelor placebo or 2) 45 mg ticagrelor + 10 mg ticagrelor placebo. Drugs taken orally, twice a day (morning and evening, at least 12 hours apart) from randomization until the end of treatment.
DrugPlacebo
10 mg ticagrelor placebo + 45 mg ticagrelor placebo. Drugs taken orally, twice a day (morning and evening at least 12 hours apart) from randomization until the end of treatment

What researchers measure

Primary outcomes

Change in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary
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

Secondary outcomes

Average of the Daily Worst Pain Values Reported Via eDiary
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
Change in Proportion of Days With Analgesic Use Measured by an eDiary
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

Other outcomes

Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients)
To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD
Time frame: Baseline through Week 12
Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events)
To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD
Time frame: Baseline through Week 12

Results

Posted Dec 14, 2017

Participant flow

This study was conducted at 26 centers in 8 countries between 09 July 2015 and 16 November 2016.

Participant flow — Overall Study
Milestone	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID
Started	30	27	30
Completed	28	24	27
Not completed	2	3	3
Withdrew: Withdrawal by subject	2	1	2
Withdrew: Did not fulfill randomization criteria	0	1	0
Withdrew: Dev. of study-spec. withdrawal criteria	0	0	1
Withdrew: Lost to follow-up	0	1	0

Outcome measures

PrimaryChange in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary

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
Reported as:: Least squares mean · Proportion of days with pain

Change in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary
Proportion of days with pain	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID
Change in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary	-0.1802 ± 0.05453	-0.1352 ± 0.05287	-0.1001 ± 0.05233

Statistical analysis

PLACEBO 10MG BID + PLACEBO 45MG BID vs TICAGRELOR 10MG BID + PLACEBO 45MG BID · Mixed Models Analysis · Mean difference (final values): 0.0450 · 90% CI -0.0610 to 0.1510
PLACEBO 10MG BID + PLACEBO 45MG BID vs TICAGRELOR 45MG BID + PLACEBO 10MG BID · Mixed Models Analysis · Mean difference (final values): 0.0801 · 90% CI -0.0230 to 0.1832

SecondaryAverage of the Daily Worst Pain Values Reported Via eDiary

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
Reported as:: Mean · Average daily worst pain rating

Average of the Daily Worst Pain Values Reported Via eDiary
Average daily worst pain rating	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID
Average of the Daily Worst Pain Values Reported Via eDiary	1.02 ± 1.106	1.15 ± 1.547	1.74 ± 2.277

SecondaryChange in Proportion of Days With Analgesic Use Measured by an eDiary

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
Reported as:: Least squares mean · Proportion of days with analgesic use

Change in Proportion of Days With Analgesic Use Measured by an eDiary
Proportion of days with analgesic use	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID
Change in Proportion of Days With Analgesic Use Measured by an eDiary	-0.1991 ± 0.08763	-0.0799 ± 0.08540	-0.1016 ± 0.08664

Statistical analysis

PLACEBO 10MG BID + PLACEBO 45MG BID vs TICAGRELOR 10MG BID + PLACEBO 45MG BID · Mixed Models Analysis · Mean difference (final values): 0.1192 · 90% CI 0.0350 to 0.2035
PLACEBO 10MG BID + PLACEBO 45MG BID vs TICAGRELOR 45MG BID + PLACEBO 10MG BID · Mixed Models Analysis · Mean difference (final values): 0.0975 · 90% CI 0.0155 to 0.1795

Other pre-specifiedNumber of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients)

To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD

Time frame:: Baseline through Week 12
Reported as:: Number · Number of patients

Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients)
Number of patients	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID
Patients with any bleeding events	2	2	2
Pts w/ any bleeding event requiring intervention	2	1	2

Other pre-specifiedNumber of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events)

To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD

Time frame:: Baseline through Week 12
Reported as:: Number · Number of events

Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events)
Number of events	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID
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

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
PLACEBO 10MG BID + PLACEBO 45MG BID	—	6/30 (20%)	16/30 (53.3%)
TICAGRELOR 10MG BID + PLACEBO 45MG BID	—	6/26 (23.1%)	15/26 (57.7%)
TICAGRELOR 45MG BID + PLACEBO 10MG BID	—	5/30 (16.7%)	20/30 (66.7%)

Most frequent serious events

Showing 10 of 14

Most frequent serious events
Event	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID
Sickle cell anaemia with crisisBlood and lymphatic system disorders	3/30	5/26	3/30
GastroenteritisInfections and infestations	2/30	0/26	1/30
Lower respiratory tract infectionInfections and infestations	0/30	1/26	0/30
ArthralgiaMusculoskeletal and connective tissue disorders	0/30	1/26	0/30
HeadacheNervous system disorders	0/30	1/26	0/30
Acute chest syndromeRespiratory, thoracic and mediastinal disorders	0/30	1/26	1/30
ReticulocytopeniaBlood and lymphatic system disorders	0/30	0/26	1/30
Local swellingGeneral disorders	1/30	0/26	0/30
Hepatic ischaemiaHepatobiliary disorders	1/30	0/26	0/30
CellulitisInfections and infestations	1/30	0/26	0/30

Most frequent other events

Showing 10 of 21

Most frequent other events
Event	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID
HeadacheNervous system disorders	8/30	11/26	8/30
ArthralgiaMusculoskeletal and connective tissue disorders	6/30	6/26	9/30
Pain in extremityMusculoskeletal and connective tissue disorders	5/30	4/26	9/30
Back painMusculoskeletal and connective tissue disorders	7/30	4/26	4/30
Abdominal painGastrointestinal disorders	3/30	5/26	3/30
Non-cardiac chest painGeneral disorders	3/30	3/26	4/30
PneumoniaInfections and infestations	2/30	2/26	4/30
Upper respiratory tract infectionInfections and infestations	4/30	1/26	1/30
Urinary tract infectionInfections and infestations	4/30	2/26	2/30
Musculoskeletal painMusculoskeletal and connective tissue disorders	2/30	3/26	3/30

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID	Total
Mean	21.6 ± 3.42	21.9 ± 2.72	23.2 ± 3.69	22.2 ± 3.35

Sex: Female, Male
Sex: Female, Male(Participants)	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID	Total
Female	16	15	16	47
Male	14	12	14	40

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	PLACEBO 10MG BID + PLACEBO 45MG BID	TICAGRELOR 10MG BID + PLACEBO 45MG BID	TICAGRELOR 45MG BID + PLACEBO 10MG BID	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	15	14	17	46
White	15	12	13	40
More than one race	0	1	0	1
Unknown or Not Reported	0	0	0	0

Study locations

20 sites

Research Site
Miami, Florida 33136, United States
Research Site
Bethesda, Maryland 20817, United States
Research Site
Charleston, South Carolina 29425, United States
Research Site
Alexandria, 21131, Egypt
Research Site
Cairo, 11562, Egypt
Research Site
Cairo, 11566, Egypt
Research Site
Bordeaux Cedex, 33076, France
Research Site
Strasbourg, 67091, France
Research Site
Verona, 37134, Italy
Research Site
Kikuyu, 00100, Kenya
Research Site
Kisian, 40100, Kenya
Research Site
Nairobi, 40100, Kenya
Research Site
Beirut, 1107 2020, Lebanon
Research Site
Beirut, 113-6044, Lebanon
Research Site
Adana, 01130, Turkey
Research Site
Mersin, 33079, Turkey
Research Site
Van, 65080, Turkey
Research Site
Harrow, HA1 3UJ, United Kingdom
Research Site
London, E1 1BB, United Kingdom
Research Site
London, E9 6SR, United Kingdom

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02482298
Lead sponsor: AstraZeneca
Responsible party: Sponsor
First posted: Jun 26, 2015
Start date: Jul 9, 2015
Primary completion: Nov 16, 2016
Completion: Nov 16, 2016
Results posted: Dec 14, 2017
Last update: Dec 19, 2018

Study contacts

Maria Ignacia -Berraondo, MD

study director · Quintiles, Inc.

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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