Trial Outcomes & Findings for Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (NCT NCT01425307)
NCT ID: NCT01425307
Last Updated: 2020-07-22
Results Overview
The primary endpoint for the TWiTCH trial was the difference between the treatment groups of the maximum TCD TAMV on the index side, calculated from a mixed model. The index side is the side with the higher mean (averaged over baseline evaluations) of the maximum (over arteries on that side) TCD time-averaged velocity. Values of the TAMV on the index site were obtained at clinic visits during baseline and during the treatment period.
TERMINATED
PHASE3
159 participants
Since the study was terminated early, time frame is from beginning of treatment until end of treatment (up to 24 Months).
2020-07-22
Participant Flow
Phase 3 First Patient In: 16-Sep-2011; Last Patient Last Visit 10-Feb-2015 26 medical institutions in the United States of America and Canada
159 were enrolled. 121 met eligibility criteria and randomized to treatment.
Participant milestones
| Measure |
Standard Therapy
Standard Therapy of monthly transfusions
|
Treatment Arm
Hydroxyurea will be provided as capsules or liquid
Hydroxyurea: Capsules (300 mg, 400 mg, or 500 mg) taken once daily or liquid formulation (100 mg/mL)
|
|---|---|---|
|
Overall Study
STARTED
|
61
|
60
|
|
Overall Study
COMPLETED
|
42
|
41
|
|
Overall Study
NOT COMPLETED
|
19
|
19
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea
Baseline characteristics by cohort
| Measure |
Standard Therapy
n=61 Participants
Standard Therapy of monthly transfusions
|
Treatment Arm
n=60 Participants
Hydroxyurea will be provided as capsules or liquid
Hydroxyurea: Capsules (300 mg, 400 mg, or 500 mg) taken once daily or liquid formulation (100 mg/mL)
|
Total
n=121 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
61 Participants
n=39 Participants
|
60 Participants
n=41 Participants
|
121 Participants
n=35 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Age, Continuous
|
9.5 years
STANDARD_DEVIATION 2.6 • n=39 Participants
|
9.7 years
STANDARD_DEVIATION 3.2 • n=41 Participants
|
9.6 years
STANDARD_DEVIATION 2.9 • n=35 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=39 Participants
|
29 Participants
n=41 Participants
|
71 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=39 Participants
|
31 Participants
n=41 Participants
|
50 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
58 Participants
n=39 Participants
|
57 Participants
n=41 Participants
|
115 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
58 Participants
n=39 Participants
|
57 Participants
n=41 Participants
|
115 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
5 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Region of Enrollment
Canada
|
4 participants
n=39 Participants
|
5 participants
n=41 Participants
|
9 participants
n=35 Participants
|
|
Region of Enrollment
United States
|
57 participants
n=39 Participants
|
55 participants
n=41 Participants
|
112 participants
n=35 Participants
|
|
Age at Index TCD
|
5.7 years
STANDARD_DEVIATION 2.0 • n=39 Participants
|
5.0 years
STANDARD_DEVIATION 1.8 • n=41 Participants
|
5.4 years
STANDARD_DEVIATION 1.9 • n=35 Participants
|
|
Duration of Transfusions
|
3.8 years
STANDARD_DEVIATION 1.8 • n=39 Participants
|
4.5 years
STANDARD_DEVIATION 2.8 • n=41 Participants
|
4.1 years
STANDARD_DEVIATION 2.4 • n=35 Participants
|
PRIMARY outcome
Timeframe: Since the study was terminated early, time frame is from beginning of treatment until end of treatment (up to 24 Months).Population: Intention-to-Treat
The primary endpoint for the TWiTCH trial was the difference between the treatment groups of the maximum TCD TAMV on the index side, calculated from a mixed model. The index side is the side with the higher mean (averaged over baseline evaluations) of the maximum (over arteries on that side) TCD time-averaged velocity. Values of the TAMV on the index site were obtained at clinic visits during baseline and during the treatment period.
Outcome measures
| Measure |
Treatment Arm
n=60 Participants
Hydroxyurea will be provided as capsules or liquid
Hydroxyurea: Capsules (300 mg, 400 mg, or 500 mg) taken once daily or liquid formulation (100 mg/mL)
|
Standard Therapy
n=61 Participants
Standard Therapy of monthly transfusions
|
|---|---|---|
|
Difference in TCD Time-averaged Mean Velocity (TAMV) on the Index Side
|
138 cm/sec
Interval 135.0 to 142.0
|
143 cm/sec
Interval 140.0 to 146.0
|
SECONDARY outcome
Timeframe: 24 monthsThis secondary endpoint for the TWiTCH trial will be maximum TCD time-averaged mean velocity on the non-index side. The non-index side is the side with the lower mean (averaged over baseline evaluations) of the maximum (over arteries on that side) TCD time-averaged velocity. Values of the secondary endpoint will be obtained at clinic visits during baseline and during the 24-month treatment period.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThis secondary outcome measure will compare standard to alternative therapy for primary stroke events (a) primary ischemic stroke; b) primary hemorrhagic stroke
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThis secondary objective will compare standard to alternative treatment for the incidence of non-stroke neurological events. Data for this outcome will be collected through entry and exit neurological exams.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and 24 monthsThis secondary objective will compare standard to alternative therapy for hepatic iron overload.
Outcome measures
| Measure |
Treatment Arm
n=61 Participants
Hydroxyurea will be provided as capsules or liquid
Hydroxyurea: Capsules (300 mg, 400 mg, or 500 mg) taken once daily or liquid formulation (100 mg/mL)
|
Standard Therapy
n=60 Participants
Standard Therapy of monthly transfusions
|
|---|---|---|
|
Change of Baseline in Hepatic Iron Overload as Assessed by Serum Ferritin
|
-38 ng per mL
Standard Deviation 2095
|
-1805 ng per mL
Standard Deviation 1651
|
SECONDARY outcome
Timeframe: 24 monthsStandard Quality of Life measure will be taken during specific time points as well as one newly developed Sickle Cell Disease-specific test.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThis outcome will be measured using Barthel Index testing at the beginning, middle, and end of the treatment period.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThis outcome will be measured using standardized neurocognitive tests at baseline and exit.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThis outcome will be measured by capturing height and weight monthly and conducting an annual pubertal assessment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThis outcome will be recorded on every interval visit form through questions asking whether there have been transfusion complications. Any complication higher than a CTCAE grade 2 event will be reported as a SAE.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 MonthsThis measure will be performed on a monthly basis throughout the trial by recording the CBC and retic count.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThis outcome will be recorded on every interval visit form through questions asking whether there have been phlebotomy complications. Any complication higher than a CTCAE grade 2 event will be reported as a SAE.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThis outcome will be recorded through questions asking whether there have been Liver MRI complications at baseline, middle, and end of treatment. Any complication higher than a CTCAE grade 2 event will be reported as a SAE.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 MonthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and 24 monthsPopulation: Participants with available data
This secondary objective will compare standard to alternative therapy for hepatic iron overload.
Outcome measures
| Measure |
Treatment Arm
n=52 Participants
Hydroxyurea will be provided as capsules or liquid
Hydroxyurea: Capsules (300 mg, 400 mg, or 500 mg) taken once daily or liquid formulation (100 mg/mL)
|
Standard Therapy
n=58 Participants
Standard Therapy of monthly transfusions
|
|---|---|---|
|
Change of Baseline in Hepatic Iron Overload as Assessed by Liver Iron Concentration
|
2.4 mg FE per g dry weight liver
Standard Deviation 8.7
|
-1.9 mg FE per g dry weight liver
Standard Deviation 4.2
|
Adverse Events
Standard Therapy
Treatment Arm
Serious adverse events
| Measure |
Standard Therapy
n=61 participants at risk
Standard Therapy of monthly transfusions
|
Treatment Arm
n=60 participants at risk
Hydroxyurea will be provided as capsules or liquid
Hydroxyurea: Capsules (300 mg, 400 mg, or 500 mg) taken once daily or liquid formulation (100 mg/mL)
|
|---|---|---|
|
Blood and lymphatic system disorders
Vaso-occlusive Pain
|
1.6%
1/61 • Number of events 3 • 2 years
|
8.3%
5/60 • Number of events 11 • 2 years
|
|
Infections and infestations
Fever
|
1.6%
1/61 • Number of events 1 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute Chest Syndrome
|
3.3%
2/61 • Number of events 3 • 2 years
|
6.7%
4/60 • Number of events 5 • 2 years
|
|
Nervous system disorders
Headache
|
0.00%
0/61 • 2 years
|
1.7%
1/60 • Number of events 2 • 2 years
|
|
Nervous system disorders
Intracranial Aneurysm
|
1.6%
1/61 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.6%
1/61 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Surgical and medical procedures
Splenomeagaly/Splenectomy
|
1.6%
1/61 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
Other adverse events
| Measure |
Standard Therapy
n=61 participants at risk
Standard Therapy of monthly transfusions
|
Treatment Arm
n=60 participants at risk
Hydroxyurea will be provided as capsules or liquid
Hydroxyurea: Capsules (300 mg, 400 mg, or 500 mg) taken once daily or liquid formulation (100 mg/mL)
|
|---|---|---|
|
Blood and lymphatic system disorders
Sickle Cell Anemia with Crisis
|
14.8%
9/61 • Number of events 28 • 2 years
|
40.0%
24/60 • Number of events 62 • 2 years
|
|
Gastrointestinal disorders
Abdominal Pain
|
11.5%
7/61 • Number of events 12 • 2 years
|
10.0%
6/60 • Number of events 7 • 2 years
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
4.9%
3/61 • Number of events 3 • 2 years
|
5.0%
3/60 • Number of events 4 • 2 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/61 • 2 years
|
6.7%
4/60 • Number of events 6 • 2 years
|
|
Gastrointestinal disorders
Gastritis
|
4.9%
3/61 • Number of events 4 • 2 years
|
0.00%
0/60 • 2 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/61 • 2 years
|
6.7%
4/60 • Number of events 7 • 2 years
|
|
Gastrointestinal disorders
Vomiting
|
6.6%
4/61 • Number of events 4 • 2 years
|
0.00%
0/60 • 2 years
|
|
General disorders
Pyrxia
|
11.5%
7/61 • Number of events 7 • 2 years
|
16.7%
10/60 • Number of events 10 • 2 years
|
|
Immune system disorders
Seasonal Allergy
|
0.00%
0/61 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Infections and infestations
Gastroenteritis
|
4.9%
3/61 • Number of events 3 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Infections and infestations
Gastrointestinal Viral Infection
|
4.9%
3/61 • Number of events 3 • 2 years
|
0.00%
0/60 • 2 years
|
|
Infections and infestations
Influenza
|
4.9%
3/61 • Number of events 4 • 2 years
|
11.7%
7/60 • Number of events 9 • 2 years
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/61 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
|
Infections and infestations
Pharyngitis Streptococcal
|
14.8%
9/61 • Number of events 12 • 2 years
|
15.0%
9/60 • Number of events 11 • 2 years
|
|
Infections and infestations
Pneumonia
|
4.9%
3/61 • Number of events 3 • 2 years
|
0.00%
0/60 • 2 years
|
|
Infections and infestations
Respiratory Syncytial Virus Infection
|
0.00%
0/61 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Infections and infestations
Sinusitis
|
0.00%
0/61 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
23.0%
14/61 • Number of events 21 • 2 years
|
30.0%
18/60 • Number of events 30 • 2 years
|
|
Infections and infestations
Urinary Tract Infection
|
9.8%
6/61 • Number of events 6 • 2 years
|
5.0%
3/60 • Number of events 4 • 2 years
|
|
Infections and infestations
Viral Infection
|
16.4%
10/61 • Number of events 11 • 2 years
|
15.0%
9/60 • Number of events 12 • 2 years
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
4.9%
3/61 • Number of events 3 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Injury, poisoning and procedural complications
Procedural Dizziness
|
0.00%
0/61 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Injury, poisoning and procedural complications
Procedural Hypotension
|
0.00%
0/61 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Injury, poisoning and procedural complications
Transfusion Reaction
|
8.2%
5/61 • Number of events 5 • 2 years
|
0.00%
0/60 • 2 years
|
|
Investigations
Alanine Aminotranferase
|
19.7%
12/61 • Number of events 16 • 2 years
|
11.7%
7/60 • Number of events 11 • 2 years
|
|
Investigations
Aspartate Aminotranserase
|
14.8%
9/61 • Number of events 11 • 2 years
|
23.3%
14/60 • Number of events 16 • 2 years
|
|
Investigations
Blood Bilirubin Increased
|
19.7%
12/61 • Number of events 37 • 2 years
|
5.0%
3/60 • Number of events 4 • 2 years
|
|
Investigations
Blood Creatinine Increased
|
0.00%
0/61 • 2 years
|
11.7%
7/60 • Number of events 8 • 2 years
|
|
Investigations
Coombs Direct Test Positive
|
11.5%
7/61 • Number of events 10 • 2 years
|
5.0%
3/60 • Number of events 4 • 2 years
|
|
Investigations
Hemoglobin Decreased
|
41.0%
25/61 • Number of events 66 • 2 years
|
53.3%
32/60 • Number of events 76 • 2 years
|
|
Investigations
Neutrophil Count Decreased
|
0.00%
0/61 • 2 years
|
25.0%
15/60 • Number of events 19 • 2 years
|
|
Investigations
Platelet Count Decreased
|
0.00%
0/61 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
|
Investigations
Reticulocyte Count Decreased
|
0.00%
0/61 • 2 years
|
20.0%
12/60 • Number of events 16 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
4.9%
3/61 • Number of events 5 • 2 years
|
0.00%
0/60 • 2 years
|
|
Nervous system disorders
Headache
|
31.1%
19/61 • Number of events 38 • 2 years
|
36.7%
22/60 • Number of events 41 • 2 years
|
|
Nervous system disorders
Migraine
|
4.9%
3/61 • Number of events 3 • 2 years
|
11.7%
7/60 • Number of events 9 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute Chest Syndrome
|
6.6%
4/61 • Number of events 4 • 2 years
|
10.0%
6/60 • Number of events 6 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/61 • 2 years
|
5.0%
3/60 • Number of events 10 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/61 • 2 years
|
6.7%
4/60 • Number of events 5 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.9%
3/61 • Number of events 4 • 2 years
|
0.00%
0/60 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Sleep Apnea Syndrome
|
4.9%
3/61 • Number of events 3 • 2 years
|
0.00%
0/60 • 2 years
|
|
Vascular disorders
Poor Venous Access
|
6.6%
4/61 • Number of events 4 • 2 years
|
0.00%
0/60 • 2 years
|
|
Nervous system disorders
Transient Ischemic Attack
|
4.9%
3/61 • Number of events 3 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
Additional Information
Barry Robert Davis
The University of Texas School of Public Health
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60