Trial Outcomes & Findings for North American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) (NCT NCT01408030)
NCT ID: NCT01408030
Last Updated: 2018-10-19
Results Overview
Bleeding episodes per week
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
123 participants
Primary outcome timeframe
Weeks 5-12 of active treatment phase
Results posted on
2018-10-19
Participant Flow
Patients were recruited from the HHT clinics at 6 sites if they met all of the following criteria: age \>=18; diagnosis of definite or possible HHT; epistaxis lasting at least 1 minute, occurring at least once weekly, and clinically stable during the preceding 8weeks; and had an Epistaxis Severity Score (ESS) of at least 3.0.
123 patients provided consent but 1 withdrew consent and 1 was excluded due to brain arteriovenous malformation. Therefore 121 patients were randomized and included in participant flow. 1 patient in the estriol group was subsequently removed after it was discovered that she was taking estrogen outside the protocol (protocol violation).
Participant milestones
| Measure |
Bevacizumab Spray
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Treatment Phase (on Drug)
STARTED
|
29
|
31
|
33
|
28
|
|
Treatment Phase (on Drug)
COMPLETED
|
26
|
24
|
32
|
25
|
|
Treatment Phase (on Drug)
NOT COMPLETED
|
3
|
7
|
1
|
3
|
|
Observation Phase (Off Drug)
STARTED
|
26
|
24
|
32
|
25
|
|
Observation Phase (Off Drug)
COMPLETED
|
22
|
18
|
26
|
21
|
|
Observation Phase (Off Drug)
NOT COMPLETED
|
4
|
6
|
6
|
4
|
Reasons for withdrawal
| Measure |
Bevacizumab Spray
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Treatment Phase (on Drug)
Lost to Follow-up
|
1
|
0
|
1
|
0
|
|
Treatment Phase (on Drug)
Lack of Efficacy
|
2
|
6
|
0
|
3
|
|
Treatment Phase (on Drug)
Protocol Violation
|
0
|
1
|
0
|
0
|
|
Observation Phase (Off Drug)
Lost to Follow-up
|
0
|
2
|
2
|
0
|
|
Observation Phase (Off Drug)
Withdrawal by Subject
|
3
|
2
|
1
|
3
|
|
Observation Phase (Off Drug)
Physician Decision
|
0
|
1
|
2
|
0
|
|
Observation Phase (Off Drug)
Other
|
1
|
1
|
1
|
1
|
Baseline Characteristics
North American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Baseline characteristics by cohort
| Measure |
Bevacizumab Spray
n=29 Participants
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
n=30 Participants
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
n=33 Participants
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
n=28 Participants
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
47.8 years
n=5 Participants
|
56.6 years
n=7 Participants
|
53 years
n=5 Participants
|
53 years
n=4 Participants
|
52.8 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
52 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
68 Participants
n=21 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
|
0 Participants
n=21 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
|
0 Participants
n=21 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
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
119 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Definite HHT
|
26 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
113 Participants
n=21 Participants
|
|
Epistaxis history
|
10.0 bleeding episodes per week
n=5 Participants
|
7.0 bleeding episodes per week
n=7 Participants
|
7.8 bleeding episodes per week
n=5 Participants
|
7.0 bleeding episodes per week
n=4 Participants
|
7.0 bleeding episodes per week
n=21 Participants
|
|
Epistaxis severity score
|
5.16 units on a scale
n=5 Participants
|
5.19 units on a scale
n=7 Participants
|
5.43 units on a scale
n=5 Participants
|
5.71 units on a scale
n=4 Participants
|
5.37 units on a scale
n=21 Participants
|
PRIMARY outcome
Timeframe: Weeks 5-12 of active treatment phasePopulation: Participants were included in this analysis (106) if they had at least 3 weeks of data during weeks 5-12; therefore the number of participants analyzed do not equal the number who finished the active treatment phase (120). 2 patients were lost to follow up, 5 dropped out before week 5, 6 filled out diaries incorrectly, and 1 had no diary.
Bleeding episodes per week
Outcome measures
| Measure |
Bevacizumab Spray
n=24 Participants
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
n=25 Participants
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
n=30 Participants
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
n=27 Participants
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Frequency of Epistaxis
|
7.0 Bleeding episodes per week
Interval 4.5 to 10.5
|
8.0 Bleeding episodes per week
Interval 4.0 to 12.0
|
7.5 Bleeding episodes per week
Interval 3.0 to 11.0
|
8.0 Bleeding episodes per week
Interval 3.0 to 14.0
|
SECONDARY outcome
Timeframe: 5-12 weeks of active treatmentPopulation: Participants were included in this analysis (112) if they had at least 3 weeks of data during weeks 5-12; therefore the number of participants analyzed do not equal the number who finished the active treatment phase (120). 2 patients were lost to follow up, 5 dropped out before week 5, and 1 had no epistaxis diary.
Total minutes of bleeding per week
Outcome measures
| Measure |
Bevacizumab Spray
n=26 Participants
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
n=26 Participants
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
n=32 Participants
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
n=28 Participants
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Duration of Epistaxis
|
23.5 Total minutes of bleeding per week
Interval 13.0 to 40.0
|
36.5 Total minutes of bleeding per week
Interval 7.0 to 70.0
|
44.5 Total minutes of bleeding per week
Interval 13.5 to 87.5
|
46 Total minutes of bleeding per week
Interval 10.0 to 84.0
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Participants were included in this analysis if they completed week 12 (phase 1) and filled out an ESS score. 1 participant each from the bevacizumab and placebo group did not fill out an ESS score at week 12.
Hoag Epistaxis Severity Score (ESS) is based on 6 nosebleed variables such as frequency and duration which are entered by patients. The ESS has a minimum value of 0 and maximum value of 10, with 10 representing more severe epistaxis.
Outcome measures
| Measure |
Bevacizumab Spray
n=25 Participants
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
n=24 Participants
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
n=32 Participants
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
n=24 Participants
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Hoag Epistaxis Severity Score
|
3.54 units on a scale (0-10)
Interval 3.0 to 4.08
|
3.56 units on a scale (0-10)
Interval 2.81 to 4.3
|
4.06 units on a scale (0-10)
Interval 3.5 to 4.61
|
3.74 units on a scale (0-10)
Interval 3.17 to 4.31
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: 8 participants who finished the active treatment phase did not have a hemoglobin level measured, and thus only 99 were analyzed.
grams/100 ml, assessed at week 12
Outcome measures
| Measure |
Bevacizumab Spray
n=23 Participants
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
n=22 Participants
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
n=31 Participants
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
n=23 Participants
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Hemoglobin Level
|
12.8 gram/100 ml
Interval 11.7 to 14.1
|
13.1 gram/100 ml
Interval 12.3 to 14.9
|
11.4 gram/100 ml
Interval 10.0 to 13.6
|
13.8 gram/100 ml
Interval 12.6 to 14.9
|
SECONDARY outcome
Timeframe: 12 weeksNumber of participants requiring RBC transfusion during weeks 1-12
Outcome measures
| Measure |
Bevacizumab Spray
n=29 Participants
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
n=30 Participants
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
n=33 Participants
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
n=28 Participants
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Number of Participants Requiring Red Blood Cell (RBC) Transfusion
|
1 Participants
|
2 Participants
|
5 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Baseline through 12 weeksTreatment failure is defined as the occurrence of one or more of the following during the study: need for nasal surgery or chemical cautery or other new treatment modality to control epistaxis; transfusion of more than 12 units of RBC; severe complications such as acute myocardial infarction, venous thromboembolism, brain hemorrhage; or death
Outcome measures
| Measure |
Bevacizumab Spray
n=29 Participants
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
n=30 Participants
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
n=33 Participants
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
n=28 Participants
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Number of Participants With Treatment Failure
|
2 Participants
|
5 Participants
|
0 Participants
|
3 Participants
|
Adverse Events
Bevacizumab Spray
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
Estriol Spray
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
Tranexamic Acid Spray
Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths
Placebo Spray
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Bevacizumab Spray
n=29 participants at risk
Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid
|
Estriol Spray
n=30 participants at risk
Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
|
Tranexamic Acid Spray
n=33 participants at risk
Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid
|
Placebo Spray
n=28 participants at risk
Sterile saline: 0.9%, 0.1 ml spray in each nostril bid
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Nasal symptoms
|
37.9%
11/29 • Number of events 11 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
40.0%
12/30 • Number of events 12 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
30.3%
10/33 • Number of events 10 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
35.7%
10/28 • Number of events 10 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
|
Nervous system disorders
Headache
|
34.5%
10/29 • Number of events 10 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
40.0%
12/30 • Number of events 12 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
30.3%
10/33 • Number of events 10 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
21.4%
6/28 • Number of events 6 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
|
Gastrointestinal disorders
Nausea/vomiting
|
13.8%
4/29 • Number of events 4 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
3.3%
1/30 • Number of events 1 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
30.3%
10/33 • Number of events 10 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
28.6%
8/28 • Number of events 8 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
|
Gastrointestinal disorders
Abdomial pain
|
17.2%
5/29 • Number of events 5 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
6.7%
2/30 • Number of events 2 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
30.3%
10/33 • Number of events 10 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
3.6%
1/28 • Number of events 1 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
|
Eye disorders
Vision problem
|
6.9%
2/29 • Number of events 2 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
6.7%
2/30 • Number of events 2 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
15.2%
5/33 • Number of events 5 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
3.6%
1/28 • Number of events 1 • Weeks 1-24
Patients were queried at various time points about a specific list of key adverse events and asked for any additional side effects that they may have experienced. Nasal symptoms included rhinorrhea, congestion and sneezing but were not monitored in such a way to allow distinction. Nausea and vomiting were not monitored in such a way to allow distinction and are reported collectively as nausea/vomiting.
|
Additional Information
James R. Gossage, MD, Medical Director of Cure HHT
Cure HHT
Phone: 706-721-6789
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place