Trial Outcomes & Findings for Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers (NCT NCT02863068)
NCT ID: NCT02863068
Last Updated: 2025-05-07
Results Overview
Assessment of tolerability was determined by evaluating the change in methemoglobin level from baseline through the end of study at week 10. Samples were collected and Methemoglobin levels were measured by co-oximetry Results are summarized by study arm using basic descriptive statistics and expressed as a percentage of the total hemoglobin in the sample.
TERMINATED
PHASE2
18 participants
Baseline through last available measurement, up to 10 weeks
2025-05-07
Participant Flow
26 patients (pts) were screened and 24 consented (one was consented twice as the IRB required a reconsent due to the time interval which had lapsed between the consent process and study initiation during COVID). Of the 24 unique pts, 2 were lost to follow up during the run-in period and 4 pts had a reduction in ulcer size by \>25%, via normal wound care, during the run-in period and were not eligible for study-defined treatment and not enrolled into the study. As such, 18 pts were enrolled.
Participant milestones
| Measure |
Placebo
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
8
|
|
Overall Study
COMPLETED
|
10
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers
Baseline characteristics by cohort
| Measure |
Placebo
n=10 Participants
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 Participants
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.2 years
STANDARD_DEVIATION 11.0 • n=93 Participants
|
47.6 years
STANDARD_DEVIATION 13.8 • n=4 Participants
|
43.5 years
STANDARD_DEVIATION 12.5 • n=27 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=93 Participants
|
8 participants
n=4 Participants
|
18 participants
n=27 Participants
|
|
Total Ulcerated Surface Area
|
11.4 cm^2
STANDARD_DEVIATION 12.3 • n=93 Participants
|
16.6 cm^2
STANDARD_DEVIATION 15.4 • n=4 Participants
|
13.7 cm^2
STANDARD_DEVIATION 13.6 • n=27 Participants
|
|
Sickle Cell Genotype
HbSS
|
10 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Sickle Cell Genotype
HbSB+
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Sickle Cell Genotype
HbSC
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sickle Cell Genotype
HbSD
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sickle Cell Genotype
HbS/O (Arab)
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Hydroxyurea Usage
No
|
4 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Hydroxyurea Usage
Yes
|
6 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Methemoglobin Levels
|
1.76 percentage of total hemoglobin
STANDARD_DEVIATION 0.635 • n=93 Participants
|
1.49 percentage of total hemoglobin
STANDARD_DEVIATION 0.698 • n=4 Participants
|
1.64 percentage of total hemoglobin
STANDARD_DEVIATION 0.658 • n=27 Participants
|
|
Visual Analog Scale (VAS) for Pain Intensity
|
5.3 score on a scale
STANDARD_DEVIATION 2.49 • n=93 Participants
|
4.28 score on a scale
STANDARD_DEVIATION 1.62 • n=4 Participants
|
4.84 score on a scale
STANDARD_DEVIATION 2.15 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline through last available measurement, up to 10 weeksPopulation: For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.
Assessment of tolerability was determined by evaluating the change in methemoglobin level from baseline through the end of study at week 10. Samples were collected and Methemoglobin levels were measured by co-oximetry Results are summarized by study arm using basic descriptive statistics and expressed as a percentage of the total hemoglobin in the sample.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 Participants
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
Assessment of Tolerability (Methemoglobin Level)
|
-0.05 percentage of total hemoglobin
Interval -0.6 to 0.4
|
0.25 percentage of total hemoglobin
Interval -0.3 to 0.4
|
PRIMARY outcome
Timeframe: From Baseline through last study visit at 10 weeksPopulation: For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.
Change in total ulcerated surface area from baseline was assessed through the last study visit at 10 weeks. Surface area measurements of the ulcer were obtained and photographed with defined lighting, distance, exposure, and camera type. Total ulcerated surface area measurements were obtained using digital planimetry and measuring the longest length and widest width of the ulcer(s). Results are summarized by study arm using basic descriptive statistics and reported in cm\^2. Negative results are indicative of a reduction in group median total ulcerated surface area from baseline and positive results are indicative of an increase in group median total ulcerated surface area from baseline.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 Participants
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
Change in Total Ulcerated Surface Area
|
-1.50 cm^2
Interval -3.9 to -0.068
|
-3.26 cm^2
Interval -12.0 to 0.987
|
PRIMARY outcome
Timeframe: From Baseline through last study visit at 10 weeksPopulation: For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.
Change in Ulcer Pain from baseline through the last study visit at 10 weeks were assessed using the Visual Analog Scale (VAS). The VAS is a widely used tool to quantify subjective pain perception over time and in this study was used to determine the efficacy of the topical sodium nitrite. Participants were asked to mark a point on a line indicating the severity of their pain on a 0-10 scale, with "0" representing "No pain" and "10" representing the "Worst possible pain." A decrease in VAS score is indicative of a reduction in ulcer pain. Scores were summarized by study arm using basic descriptive statistics.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 Participants
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
Change in Ulcer Pain
|
-0.5 score on a scale
Interval -2.7 to 1.2
|
0.9 score on a scale
Interval -3.8 to 2.6
|
PRIMARY outcome
Timeframe: From Baseline through last study visit at 10 weeksPopulation: For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.
The number of participants who achieved an objective reduction in total surface area of the ulcer of \>= 25% from baseline is summarized and reported as a dichotomous ("No" or "Yes") variable.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 Participants
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
Number of Participants With Total Ulcerated Surface Area Reduction
No
|
5 Participants
|
4 Participants
|
|
Number of Participants With Total Ulcerated Surface Area Reduction
Yes
|
5 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: From Baseline through last study visit at 10 weeksPopulation: Number of participants analyzed identified in table below. For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.
Hydroxyurea effect on Assessment of Tolerability, as determined by the change in Methemoglobin level, was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Samples were collected and Methemoglobin levels were measured by co-oximetry. Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized as an increased or decreased percentage by study arm and analyzed using Wilcoxon-Mann-Whitney statistical testing.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 Participants
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
Hydroxyurea Effect on Assessment of Tolerability
HU
|
-0.6 percentage of total hemoglobin
Interval -0.7 to -0.4
|
0.2 percentage of total hemoglobin
Interval 0.0 to 0.3
|
|
Hydroxyurea Effect on Assessment of Tolerability
No HU
|
0.3 percentage of total hemoglobin
Interval 0.0 to 0.5
|
0.3 percentage of total hemoglobin
Interval -0.6 to 0.5
|
SECONDARY outcome
Timeframe: From Baseline through last study visit at 10 weeksPopulation: Number of participants analyzed identified in table below. For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.
Hydroxyurea effect on Change in Total Ulcerated Surface Area was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Surface area measurements of the ulcer were obtained and photographed with defined lighting, distance, exposure, and camera type. Total ulcerated surface area measurements were obtained using digital planimetry and measuring the longest length and widest width of the ulcer(s). Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized by study arm as an increase or decrease in total ulcerated surface area in cm\^2 and analyzed using Wilcoxon-Mann-Whitney and Fisher Exact statistical testing. Negative results are indicative of a reduction in group median total ulcerated surface area from baseline and positive results are indicative of an increase in group median total ulcerated surface area from baseline (with or without Hydroxyurea).
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 Participants
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
Hydroxyurea Effect on Change in Total Ulcerated Surface Area
HU
|
-1.34 cm^2
Interval -1.592 to -0.068
|
-3.506 cm^2
Interval -6.97 to -3.013
|
|
Hydroxyurea Effect on Change in Total Ulcerated Surface Area
No HU
|
-2.081 cm^2
Interval -3.897 to -1.412
|
-0.57 cm^2
Interval -17.04 to 2.031
|
SECONDARY outcome
Timeframe: From Baseline through last study visit at 10 weeksPopulation: Number of participants analyzed identified in table below. For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.
Hydroxyurea effect on change in Ulcer Pain was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Ulcer pain assessments were conducted using the Visual Analog Scale (VAS). The VAS is used to quantify subjective pain perception over time and in this study was used to determine the efficacy of the topical sodium nitrite. Participants were asked to mark a point on a line indicating the severity of their pain on a 0-10 scale, with "0" representing "No pain" and "10" representing the "Worst possible pain." Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized by study arm as an increase or decrease in ulcer pain and analyzed using Wilcoxon-Mann-Whitney statistical testing. Negative results are indicative of a decrease in group median ulcer pain from baseline and positive results are indicative of an increase in group median ulcer pain from baseline (with or without Hydroxyurea).
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 Participants
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
Hydroxyurea Effect on Change in Ulcer Pain
HU
|
0.35 score on a scale
Interval -1.25 to 2.1
|
0.9 score on a scale
Interval -5.0 to 2.4
|
|
Hydroxyurea Effect on Change in Ulcer Pain
No HU
|
-2.70 score on a scale
Interval -4.0 to 0.0
|
1.0 score on a scale
Interval -2.2 to 4.1
|
Adverse Events
Placebo
Topical Sodium Nitrite
Serious adverse events
| Measure |
Placebo
n=10 participants at risk
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 participants at risk
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
General disorders
Vaso-occlusive Crisis
|
30.0%
3/10 • Number of events 4 • Up to 10 weeks
|
25.0%
2/8 • Number of events 7 • Up to 10 weeks
|
|
Infections and infestations
Ulcer Infection
|
0.00%
0/10 • Up to 10 weeks
|
12.5%
1/8 • Number of events 1 • Up to 10 weeks
|
|
Blood and lymphatic system disorders
Acute Myeloid Leukemia
|
10.0%
1/10 • Number of events 1 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
Other adverse events
| Measure |
Placebo
n=10 participants at risk
Participants will receive placebo and standard of care
Placebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.
|
Topical Sodium Nitrite
n=8 participants at risk
Participants will receive 2% topical sodium nitrite cream and standard of care
Topical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.
|
|---|---|---|
|
General disorders
Vaso-occlusive Crisis
|
0.00%
0/10 • Up to 10 weeks
|
37.5%
3/8 • Up to 10 weeks
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Up to 10 weeks
|
12.5%
1/8 • Up to 10 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/10 • Up to 10 weeks
|
12.5%
1/8 • Up to 10 weeks
|
|
Musculoskeletal and connective tissue disorders
Chest Wall Pain
|
10.0%
1/10 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
|
Infections and infestations
Upper Respiratory Infection
|
10.0%
1/10 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
10.0%
1/10 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
|
Infections and infestations
Ulcer Infection
|
20.0%
2/10 • Up to 10 weeks
|
12.5%
1/8 • Up to 10 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
1/10 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
10.0%
1/10 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
|
Blood and lymphatic system disorders
Abnormal Blood Smear
|
10.0%
1/10 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
|
Investigations
Critical Low Lab Value
|
10.0%
1/10 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
|
Cardiac disorders
Palpitations
|
10.0%
1/10 • Up to 10 weeks
|
0.00%
0/8 • Up to 10 weeks
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/10 • Up to 10 weeks
|
12.5%
1/8 • Up to 10 weeks
|
|
General disorders
Body Ache
|
0.00%
0/10 • Up to 10 weeks
|
12.5%
1/8 • Up to 10 weeks
|
Additional Information
Dr. Caterina Minniti
Albert Einstein College of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place