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Trial Outcomes & Findings for Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency (NCT NCT03008915)

NCT ID: NCT03008915

Last Updated: 2021-02-17

Results Overview

Pulmonary microvascular blood flow is measured on contrast-enhanced MRI, limited to blood flow in the 2cm periphery of the lung

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

2 weeks

Results posted on

2021-02-17

Participant Flow

Participant milestones

Participant milestones
Measure
Aspirin First, Then Placebo
Aspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks Aspirin: 81mg aspirin taken once per day in the morning Placebo: placebo taken once per day in the morning Withdrawal from alpha1 antitrypsin replacement therapy: After the completion of the randomization to aspirin and placebo, participants who are on alpha1 replacement therapy are asked to withhold their usual alpha1 antitrypsin replacement therapy for 5 weeks. This is not randomized.
Placebo First, Then Aspirin
Placebo for 2 weeks followed by a washout period and then aspirin 81mg for 2 weeks Aspirin: 81mg aspirin taken once per day in the morning Placebo: placebo taken once per day in the morning Withdrawal from alpha1 antitrypsin replacement therapy: After the completion of the randomization to aspirin and placebo, participants who are on alpha1 replacement therapy are asked to withhold their usual alpha1 antitrypsin replacement therapy for 5 weeks. This is not randomized.
Treatment 1
STARTED
8
7
Treatment 1
COMPLETED
8
6
Treatment 1
NOT COMPLETED
0
1
Treatment 2
STARTED
8
6
Treatment 2
COMPLETED
8
6
Treatment 2
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Aspirin First, Then Placebo
Aspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks Aspirin: 81mg aspirin taken once per day in the morning Placebo: placebo taken once per day in the morning Withdrawal from alpha1 antitrypsin replacement therapy: After the completion of the randomization to aspirin and placebo, participants who are on alpha1 replacement therapy are asked to withhold their usual alpha1 antitrypsin replacement therapy for 5 weeks. This is not randomized.
Placebo First, Then Aspirin
Placebo for 2 weeks followed by a washout period and then aspirin 81mg for 2 weeks Aspirin: 81mg aspirin taken once per day in the morning Placebo: placebo taken once per day in the morning Withdrawal from alpha1 antitrypsin replacement therapy: After the completion of the randomization to aspirin and placebo, participants who are on alpha1 replacement therapy are asked to withhold their usual alpha1 antitrypsin replacement therapy for 5 weeks. This is not randomized.
Treatment 1
Withdrawal by Subject
0
1

Baseline Characteristics

1 participant withdrew before CT scan

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Overall Study
n=15 Participants
Baseline characteristics reported for all 15 participants in the crossover study.
Age, Continuous
55.6 years
STANDARD_DEVIATION 7.9 • n=15 Participants
Sex: Female, Male
Female
5 Participants
n=15 Participants
Sex: Female, Male
Male
10 Participants
n=15 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=15 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
15 Participants
n=15 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=15 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=15 Participants
Race (NIH/OMB)
Asian
0 Participants
n=15 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=15 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=15 Participants
Race (NIH/OMB)
White
15 Participants
n=15 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=15 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=15 Participants
Region of Enrollment
United States
15 participants
n=15 Participants
Smoking status
Former smoker
9 Participants
n=15 Participants
Smoking status
Never smoker
6 Participants
n=15 Participants
FEV1/FVC ratio
44.0 percent
STANDARD_DEVIATION 13.0 • n=15 Participants
Percent emphysema, -950 HU
21.2 percent
STANDARD_DEVIATION 9.8 • n=14 Participants • 1 participant withdrew before CT scan

PRIMARY outcome

Timeframe: 2 weeks

Population: Due to errors in acquisition of MRI, a number of participants had uninterpretable scans. 13 participants had MRIs interpretable for PMBF on placebo, and 7 on aspirin. Altogether, there were 6 participants with paired results from the two scans.

Pulmonary microvascular blood flow is measured on contrast-enhanced MRI, limited to blood flow in the 2cm periphery of the lung

Outcome measures

Outcome measures
Measure
Aspirin
n=6 Participants
Assessment on aspirin 81mg for 2 weeks.
Placebo
n=6 Participants
Assessment on placebo for 2 weeks.
Pulmonary Microvascular Blood Flow, Mean
36.9 mL blood/minute per 100mL lung
Standard Deviation 13.0
35.1 mL blood/minute per 100mL lung
Standard Deviation 15.4

SECONDARY outcome

Timeframe: 2 weeks

Population: Due to lab closure and technician availability, only the first 3 participants had EMPs measured.

Endothelial microparticles (EMPs) are vesicles shed from endothelial plasma membranes into the circulation in response to endothelial cell perturbation. CD31+ is a measure of apoptotic endothelial microparticles, CD62+ (P-selectin) is a measure of endothelial activation, and Annexin V/CD31+ is a more specific marker of endothelial cell apoptosis.

Outcome measures

Outcome measures
Measure
Aspirin
n=3 Participants
Assessment on aspirin 81mg for 2 weeks.
Placebo
n=2 Participants
Assessment on placebo for 2 weeks.
Endothelial Microparticles
CD31+
749.0 EMPs/uL
Standard Deviation 231.1
821.5 EMPs/uL
Standard Deviation 3.5
Endothelial Microparticles
CD62+
1357.3 EMPs/uL
Standard Deviation 469.6
596 EMPs/uL
Standard Deviation 287.1
Endothelial Microparticles
Annexin V, CD31+
145.0 EMPs/uL
Standard Deviation 62.8
317.0 EMPs/uL
Standard Deviation 210.7

SECONDARY outcome

Timeframe: 5 weeks

Population: Only 2 participants had EMPs measured on placebo and 2 off AAT replacement therapy, only 1 participant had EMPs measured at both time points.

Endothelial microparticles (EMPs) are vesicles shed from endothelial plasma membranes into the circulation in response to endothelial cell perturbation. CD31+ is a measure of apoptotic endothelial microparticles, CD62+ (P-selectin) is a measure of endothelial activation, and Annexin V/CD31+ is a more specific marker of endothelial cell apoptosis.

Outcome measures

Outcome measures
Measure
Aspirin
n=2 Participants
Assessment on aspirin 81mg for 2 weeks.
Placebo
n=2 Participants
Assessment on placebo for 2 weeks.
Endothelial Microparticles
CD31+
996.0 EMPs/uL
Standard Deviation 408.7
821.5 EMPs/uL
Standard Deviation 3.5
Endothelial Microparticles
CD62+
3681.5 EMPs/uL
Standard Deviation 3806.4
596.0 EMPs/uL
Standard Deviation 287.1
Endothelial Microparticles
Annexin V, CD31+
146.0 EMPs/uL
Standard Deviation 186.7
317.0 EMPs/uL
Standard Deviation 210.7

SECONDARY outcome

Timeframe: 5 weeks

Population: 2 participants who completed the withdrawal phase had MRIs interpretable for PMBF on placebo and off AAT replacement therapy, data for the other 2 participants was uninterpretable for at least 1 of the 2 scans.

Pulmonary microvascular blood flow is measured on contrast-enhanced MRI in the peripheral 2cm of the lung.

Outcome measures

Outcome measures
Measure
Aspirin
n=2 Participants
Assessment on aspirin 81mg for 2 weeks.
Placebo
n=13 Participants
Assessment on placebo for 2 weeks.
Pulmonary Microvascular Blood Flow, Mean
35.5 mL blood/minute per 100mL lung
Standard Deviation 2.6
35.1 mL blood/minute per 100mL lung
Standard Deviation 11.0

Adverse Events

Aspirin

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Aspirin
n=14 participants at risk
Assessment on aspirin 81mg for 2 weeks.
Placebo
n=15 participants at risk
Assessment on placebo for 2 weeks.
Vascular disorders
Syncope
0.00%
0/14 • During the course of the study, typically this was 6 weeks, but up to 11 weeks for those also withheld their alpha-1 antitrypsin replacement therapy.
6.7%
1/15 • Number of events 1 • During the course of the study, typically this was 6 weeks, but up to 11 weeks for those also withheld their alpha-1 antitrypsin replacement therapy.

Additional Information

Dr. Carrie Pistenmaa

Columbia University

Phone: 212-342-4162

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place