Trial Outcomes & Findings for Anticoagulation For Pulmonary Hypertension in Sickle Cell Disease (NCT NCT01036802)

Results Overview

We determined the effect of anticoagulation with warfarin on estimated pulmonary artery systolic pressure obtained by Doppler echocardiography. The presented data are average values for the study subjects in the treatment group. When data was missing, the previous value was carried forward.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Measurements were obtained at Screening, and at Months 3, 6, 9, and 12

Results posted on

2016-05-09

Participant Flow

Patients were randomized 1:1 to receive anticoagulation with warfarin or placebo after evaluation in the clinical and translational research center. Enrollment began in January 2010 and ended in September 2012 due to poor patient accrual.

Following patient identification, an open-label run-in period was begun to ensure patient doses of warfarin could be titrated to a stable level that achieved an international normalized ratio between 2.0 and 3.0 without exceeding a dose of 15 mg per day and to exclude patients with a level of compliance less than 80% (based on pill counts).

Participant milestones

Participant milestones
Measure	Warfarin Patients on the active treatment arm will be anticoagulated using the vitamin K antagonist, warfarin	Placebo Patients were randomized to placebo
Overall Study STARTED	2	1
Overall Study COMPLETED	2	1
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Anticoagulation For Pulmonary Hypertension in Sickle Cell Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Warfarin n=2 Participants Patients on the active treatment arm will be anticoagulated using the vitamin K antagonist, warfarin	Placebo n=1 Participants Patients were randomized to placebo	Total n=3 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Continuous	29.5 years STANDARD_DEVIATION 12.02 • n=99 Participants	53 years n=107 Participants	37.3 years STANDARD_DEVIATION 16.01 • n=206 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants

PRIMARY outcome

Timeframe: Measurements were obtained at Screening, and at Months 3, 6, 9, and 12

We determined the effect of anticoagulation with warfarin on estimated pulmonary artery systolic pressure obtained by Doppler echocardiography. The presented data are average values for the study subjects in the treatment group. When data was missing, the previous value was carried forward.

Outcome measures

Outcome measures
Measure	Warfarin n=2 Participants Patients on the active treatment arm will be anticoagulated using the vitamin K antagonist, warfarin	Placebo n=1 Participants Patients were randomized to placebo
Effect of Anticoagulation on Pulmonary Artery Systolic Pressure Was Obtained by Doppler Echocardiography Screening (n=2,1)	41.3 mm Hg Full Range 0 • Interval 39.0 to 43.6	43.6 mm Hg Full Range 0 • Interval 43.6 to 43.6
Effect of Anticoagulation on Pulmonary Artery Systolic Pressure Was Obtained by Doppler Echocardiography Month 3 (n=1,1)	39.2 mm Hg Interval 39.2 to 39.2	39.2 mm Hg Interval 39.2 to 39.2
Effect of Anticoagulation on Pulmonary Artery Systolic Pressure Was Obtained by Doppler Echocardiography Month 6 (n=2,1)	41.3 mm Hg Interval 39.2 to 43.6	43.6 mm Hg Interval 43.6 to 43.6
Effect of Anticoagulation on Pulmonary Artery Systolic Pressure Was Obtained by Doppler Echocardiography Month 9 (n=1,1)	46 mm Hg Interval 46.0 to 46.0	37 mm Hg Interval 37.0 to 37.0
Effect of Anticoagulation on Pulmonary Artery Systolic Pressure Was Obtained by Doppler Echocardiography Month 12 (n=1,1)	46 mm Hg Interval 46.0 to 46.0	37 mm Hg Interval 37.0 to 37.0

SECONDARY outcome

Timeframe: Measurements were obtained at Screening, Months 3, 6, 9, and 12

We evaluated the distance walked over 6 minutes. The presented data are average values for the study subjects in the treatment group. When data was missing, the previous value was carried forward.

Outcome measures

Outcome measures
Measure	Warfarin n=2 Participants Patients on the active treatment arm will be anticoagulated using the vitamin K antagonist, warfarin	Placebo n=1 Participants Patients were randomized to placebo
6-minute Walk Test Screen (n=1,1)	1381 feet Full Range 0 • Interval 1381.0 to 1381.0	1135 feet Full Range 0 • Interval 1135.0 to 1135.0
6-minute Walk Test Month 3 (n=1,1)	1275 feet Interval 1275.0 to 1275.0	1135 feet Interval 1135.0 to 1135.0
6-minute Walk Test Month 6 (n=1,1)	1275 feet Interval 1275.0 to 1275.0	1075 feet Interval 1075.0 to 1075.0
6-minute Walk Test Month 9 (n=1,1)	1275 feet Interval 1275.0 to 1275.0	1075 feet Interval 1075.0 to 1075.0
6-minute Walk Test Month 12 (n=1,1)	1275 feet Interval 1275.0 to 1275.0	1075 feet Interval 1075.0 to 1075.0

SECONDARY outcome

Timeframe: Measurements were obtained at Screening, and at Months 3, 6, 9, and 12

Population: No analysis was performed due to the early termination of the study and the very small number of participating subjects.

We evaluated the effect of warfarin on a plasma measure of thrombin generation (thrombin-antithrombin complex)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measurements were obtained at Screening, Prior to Run-in, and at Months 3, 6, 9, and 12

Population: No analysis was performed due to the early termination of the study and the very small number of participating subjects.

We evaluated the effect of anticoagulation with warfarin on platelet activation assessed by measuring plasma levels of soluble CD40 ligand

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measurements were obtained at Screening, and at Months 3, 6, 9, and 12

Population: As the number of subjects studied were very few, requiring discontinuation of the study, evaluation of endothelial activation was not performed.

We assessed the effect of warfarin on plasma measures of endothelial activation (soluble vascular cell adhesion molecule-1)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessment was obtained until completion of study at 12 months

We assessed the effect of warfarin on mortality in the study subjects

Outcome measures

Outcome measures
Measure	Warfarin n=2 Participants Patients on the active treatment arm will be anticoagulated using the vitamin K antagonist, warfarin	Placebo n=1 Participants Patients were randomized to placebo
All-cause Mortality	0 participants	0 participants

SECONDARY outcome

Timeframe: Evaluations were obtained at Screening, and at Months 3, 6, 9, and 12

We evaluated the safety of warfarin by evaluating for major and minor bleeding complications in study subjects

Outcome measures

Outcome measures
Measure	Warfarin n=2 Participants Patients on the active treatment arm will be anticoagulated using the vitamin K antagonist, warfarin	Placebo n=1 Participants Patients were randomized to placebo
Major and Minor Bleeding Complications Screen	0 participants	0 participants
Major and Minor Bleeding Complications Month 3	0 participants	0 participants
Major and Minor Bleeding Complications Month 6	0 participants	0 participants
Major and Minor Bleeding Complications Month 9	0 participants	0 participants
Major and Minor Bleeding Complications Month 12	0 participants	0 participants

Adverse Events

Warfarin

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Warfarin n=2 participants at risk Patients on the active treatment arm will be anticoagulated using the vitamin K antagonist, warfarin	Placebo n=1 participants at risk Patients were randomized to placebo
Blood and lymphatic system disorders Delayed hemolytic transfusion reaction	50.0% 1/2 • Number of events 1 • 2 years	0.00% 0/1 • 2 years

Other adverse events

Adverse event data not reported

Additional Information

Kenneth I. Ataga, MD

University of North Carolina, Chapel Hill

Phone: 919-843-7708

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place