Trial Outcomes & Findings for NOrth American Study for the Treatment of Recurrent epIstaxis With DoxycycLine: The NOSTRIL Trial (NCT NCT04167085)
NCT ID: NCT04167085
Last Updated: 2022-07-20
Results Overview
Change in number of bleeding episodes per week by participant self-report via nosebleed diary
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
26 participants
Primary outcome timeframe
Baseline, post-washout - approximately 6 months
Results posted on
2022-07-20
Participant Flow
Participant milestones
| Measure |
Doxycycline, Then Placebo
Doxycycline for a period of 2 months followed by a 1-month washout period, and then placebo for a further 2 months period followed by a 1-month washout period.
Doxycycline: Doxycycline, 100 mg twice a day for 2 months
Placebo: Matching placebo, twice a day for 2 months
|
Placebo, Then Doxycycline
Placebo for a period of 2 months followed by a 1-month washout period, and then Doxycycline for a further 2 months period followed by a 1-month washout period.
Doxycycline: Doxycycline, 100 mg twice a day for 2 months
Placebo: Matching placebo, twice a day for 2 months
|
|---|---|---|
|
Baseline
STARTED
|
13
|
13
|
|
Baseline
Day 1
|
12
|
12
|
|
Baseline
COMPLETED
|
11
|
12
|
|
Baseline
NOT COMPLETED
|
2
|
1
|
|
First Intervention (2 Months)
STARTED
|
11
|
12
|
|
First Intervention (2 Months)
COMPLETED
|
11
|
12
|
|
First Intervention (2 Months)
NOT COMPLETED
|
0
|
0
|
|
Washout (1 Month)
STARTED
|
10
|
12
|
|
Washout (1 Month)
COMPLETED
|
10
|
12
|
|
Washout (1 Month)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention (2 Months)
STARTED
|
10
|
12
|
|
Second Intervention (2 Months)
COMPLETED
|
10
|
12
|
|
Second Intervention (2 Months)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Doxycycline, Then Placebo
Doxycycline for a period of 2 months followed by a 1-month washout period, and then placebo for a further 2 months period followed by a 1-month washout period.
Doxycycline: Doxycycline, 100 mg twice a day for 2 months
Placebo: Matching placebo, twice a day for 2 months
|
Placebo, Then Doxycycline
Placebo for a period of 2 months followed by a 1-month washout period, and then Doxycycline for a further 2 months period followed by a 1-month washout period.
Doxycycline: Doxycycline, 100 mg twice a day for 2 months
Placebo: Matching placebo, twice a day for 2 months
|
|---|---|---|
|
Baseline
Withdrawal by Subject
|
2
|
1
|
|
Washout (1 Month)
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
NOrth American Study for the Treatment of Recurrent epIstaxis With DoxycycLine: The NOSTRIL Trial
Baseline characteristics by cohort
| Measure |
Doxycycline, Then Placebo
n=13 Participants
Doxycycline for a period of 2 months followed by a 1-month washout period, and then placebo for a further 2 months period followed by a 1-month washout period.
Doxycycline: Doxycycline, 100 mg twice a day for 2 months
Placebo: Matching placebo, twice a day for 2 months
|
Placebo, Then Doxycycline
n=13 Participants
Placebo for a period of 2 months followed by a 1-month washout period, and then Doxycycline for a further 2 months period followed by a 1-month washout period.
Doxycycline: Doxycycline, 100 mg twice a day for 2 months
Placebo: Matching placebo, twice a day for 2 months
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Age, Continuous
|
51.3 years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
63.6 years
STANDARD_DEVIATION 13.8 • n=7 Participants
|
57.4 years
STANDARD_DEVIATION 14.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
13 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Epistaxis Severity Scale (ESS) score
|
6.3 Score on a scale
STANDARD_DEVIATION 1.2 • n=5 Participants
|
5.7 Score on a scale
STANDARD_DEVIATION 1.5 • n=7 Participants
|
6.0 Score on a scale
STANDARD_DEVIATION 1.4 • n=5 Participants
|
|
Quality of Life
SF-12 Physical
|
43.6 Score on a scale
STANDARD_DEVIATION 10.7 • n=5 Participants
|
40.2 Score on a scale
STANDARD_DEVIATION 9.7 • n=7 Participants
|
41.9 Score on a scale
STANDARD_DEVIATION 10.2 • n=5 Participants
|
|
Quality of Life
SF-12 Mental
|
47.0 Score on a scale
STANDARD_DEVIATION 12.5 • n=5 Participants
|
54.4 Score on a scale
STANDARD_DEVIATION 6.4 • n=7 Participants
|
50.7 Score on a scale
STANDARD_DEVIATION 10.4 • n=5 Participants
|
|
Hemoglobin level
|
12.8 g/dl
STANDARD_DEVIATION 2.5 • n=5 Participants
|
12.3 g/dl
STANDARD_DEVIATION 2.4 • n=7 Participants
|
12.5 g/dl
STANDARD_DEVIATION 2.4 • n=5 Participants
|
|
Ferritin Level
|
71.1 ng/ml
STANDARD_DEVIATION 83.7 • n=5 Participants
|
98.1 ng/ml
STANDARD_DEVIATION 186.3 • n=7 Participants
|
85.1 ng/ml
STANDARD_DEVIATION 144.1 • n=5 Participants
|
|
Number of monthly iron infusions
No infusions
|
9 participants
n=5 Participants
|
11 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Number of monthly iron infusions
1 infusion
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Number of monthly iron infusions
2 infusions
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Number of monthly iron infusions
Not reported
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Number of monthly blood transfusions
0 transfusions
|
12 participants
n=5 Participants
|
12 participants
n=7 Participants
|
24 participants
n=5 Participants
|
|
Number of monthly blood transfusions
1 transfusion
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Number of monthly blood transfusions
Not reported
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, post-washout - approximately 6 monthsPopulation: All participants who received each intervention and completed all study visits were included in the efficacy analysis
Change in number of bleeding episodes per week by participant self-report via nosebleed diary
Outcome measures
| Measure |
Doxycycline
n=22 Participants
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 Participants
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Frequency of Epistaxis
|
-1.68 Nosebleeds per week
Standard Deviation 6.55
|
1.14 Nosebleeds per week
Standard Deviation 4.44
|
PRIMARY outcome
Timeframe: Baseline, post-washout - approximately 6 monthsPopulation: All participants who received each intervention and completed all study visits were included in the efficacy analysis
Change in duration of bleeding per week by patient self-report via nosebleed diary
Outcome measures
| Measure |
Doxycycline
n=22 Participants
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 Participants
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Duration of Epistaxis
|
-41.17 Minutes per week
Standard Deviation 159.26
|
24.36 Minutes per week
Standard Deviation 58.03
|
PRIMARY outcome
Timeframe: Baseline, post-washout - approximately 6-monthsPopulation: All participants who received each intervention and completed all study visits were included in the efficacy analysis
Epistaxis Severity Scale (ESS) for Hereditary Hemorrhagic Telangiectasia, is based on 6 nosebleed variables such as frequency and duration which are reported by patients.The ESS has a minimum value of 0 and maximum value of 10, with 10 representing more severe epistaxis.
Outcome measures
| Measure |
Doxycycline
n=22 Participants
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 Participants
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Change in Severity of Epistaxis
|
-.095 score on a scale
Standard Deviation 1.55
|
-0.32 score on a scale
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: Baseline, post-washout - approximately 6 monthsPopulation: All participants who received each intervention and completed all study visits were included in the efficacy analysis
The 12-item Short Form (SF-12) is a survey designed for use with patients with multiple chronic conditions. This 12-item scale can be used to assess the physical and mental health of respondents. 10 of the 12 questions are answered on a 5-point Likert scale and 2 are answered on a 3-point Likert scale. The questions are then scored and weighted into 2 subscales, physical health and mental health. Respondents can have a score that ranges from 0-100 with 100 being the best score and indicating high physical or mental health.
Outcome measures
| Measure |
Doxycycline
n=22 Participants
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 Participants
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Change in Quality of Life
SF-12 Physical
|
2.21 score on a scale
Standard Deviation 6.94
|
-0.83 score on a scale
Standard Deviation 6.72
|
|
Change in Quality of Life
SF-12 Mental
|
-0.63 score on a scale
Standard Deviation 9.97
|
-0.63 score on a scale
Standard Deviation 9.74
|
SECONDARY outcome
Timeframe: Baseline, post-washout - approximately 6 monthsPopulation: All participants who received each intervention and completed all study visits were included in the efficacy analysis
Outcome measures
| Measure |
Doxycycline
n=22 Participants
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 Participants
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Change in Ferritin Level
|
14.9 ng/ml
Standard Deviation 72.82
|
-47.4 ng/ml
Standard Deviation 214.83
|
SECONDARY outcome
Timeframe: Baseline, post-washout (approximately 6 months)Population: All participants who received each intervention and completed all study visits were included in the efficacy analysis
Outcome measures
| Measure |
Doxycycline
n=22 Participants
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 Participants
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Change in Hemoglobin Level
|
0.26 g/dl
Standard Deviation 1.09
|
-0.12 g/dl
Standard Deviation 1.19
|
SECONDARY outcome
Timeframe: Baseline, post-washout (approximately 6 months)Population: All participants who received each intervention and completed all study visits were included in the efficacy analysis
Outcome measures
| Measure |
Doxycycline
n=22 Participants
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 Participants
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Change in Monthly Units of Packed Red Blood Cells (PRBCs) Transfused
|
0 count of PBRC units
Standard Deviation 0.31
|
0 count of PBRC units
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline, post-washout (approximately 6 months)Population: All participants who received each intervention and completed all study visits were included in the efficacy analysis
Treatment failure, defined as need for nasal surgery or other epistaxis treatments
Outcome measures
| Measure |
Doxycycline
n=22 Participants
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 Participants
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Incidence of Treatment Failure
|
0 Participants
|
1 Participants
|
Adverse Events
Doxycycline
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Doxycycline
n=23 participants at risk
Participants who received Doxycycline, 100 mg twice a day for 2 months in either the first or second intervention period of the study
|
Placebo
n=22 participants at risk
Participants who received placebo (matching Doxycycline 100mg) twice a day for 2 months in either the first or second intervention period of the study.
|
|---|---|---|
|
Gastrointestinal disorders
GI bleeding
|
0.00%
0/23 • Baseline, post-washout (approximately 6 months)
|
4.5%
1/22 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
|
Infections and infestations
Flu-like symptoms
|
0.00%
0/23 • Baseline, post-washout (approximately 6 months)
|
4.5%
1/22 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Prolonged nosebleed requiring cauterization
|
0.00%
0/23 • Baseline, post-washout (approximately 6 months)
|
4.5%
1/22 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
|
Infections and infestations
Pneumonia hospitalization
|
0.00%
0/23 • Baseline, post-washout (approximately 6 months)
|
4.5%
1/22 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Allergy-like symptoms
|
0.00%
0/23 • Baseline, post-washout (approximately 6 months)
|
4.5%
1/22 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
|
Infections and infestations
Throat infection
|
0.00%
0/23 • Baseline, post-washout (approximately 6 months)
|
4.5%
1/22 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic lung cancer dx
|
4.3%
1/23 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
0.00%
0/22 • Baseline, post-washout (approximately 6 months)
|
|
Infections and infestations
Sinus infection
|
4.3%
1/23 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
0.00%
0/22 • Baseline, post-washout (approximately 6 months)
|
|
Infections and infestations
Foot infection
|
4.3%
1/23 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
0.00%
0/22 • Baseline, post-washout (approximately 6 months)
|
|
Eye disorders
Blurred vision
|
4.3%
1/23 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
0.00%
0/22 • Baseline, post-washout (approximately 6 months)
|
|
Gastrointestinal disorders
Emesis
|
4.3%
1/23 • Number of events 4 • Baseline, post-washout (approximately 6 months)
|
0.00%
0/22 • Baseline, post-washout (approximately 6 months)
|
|
Infections and infestations
Pneumonia
|
4.3%
1/23 • Number of events 1 • Baseline, post-washout (approximately 6 months)
|
0.00%
0/22 • Baseline, post-washout (approximately 6 months)
|
Additional Information
Justin P. McWilliams, MD, FSIR
David Geffen School of Medicine at UCLA
Phone: (310) 267-8773
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place