Trial Outcomes & Findings for A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome (NCT NCT00537290)
NCT ID: NCT00537290
Last Updated: 2017-10-31
Results Overview
Serious and non-serious adverse events were evaluated throughout 52 weeks + additional 4 months for the patients with low B cell counts.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
19 participants
Primary outcome timeframe
52 weeks + additional 4 months if needed
Results posted on
2017-10-31
Participant Flow
Patients who were ≥18 years of age, did not have other systemic autoimmune diseases, and fulfilled at least one of the laboratory criteria and one of the clinical criteria were eligible for inclusion in the study.
Laboratory criteria defined as positive results of a LAC test, positive aCL IgG/IgM/IgA isotype (≥40), and/or positive anti-β2GPI IgG/IgM/IgA isotype (≥40) on 2 or more occasions, at least 12 weeks apart. Clinical criteria defined as 1)persistent thrombocytopenia 2)Cardiovascular disease 3)skin ulcer 4)aPL nephropathy 5) cognitive dysfunction.
Participant milestones
| Measure |
Rituximab
All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.
Rituximab: Rituximab 1000mg IV on Days 0 and 15
|
|---|---|
|
Overall Study
STARTED
|
19
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome
Baseline characteristics by cohort
| Measure |
Rituximab
n=19 Participants
All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.
Rituximab: Rituximab 1000mg IV on Days 0 and 15
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
40.5 years
STANDARD_DEVIATION 13.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 52 weeks + additional 4 months if neededPopulation: All patients enrolled in the study.
Serious and non-serious adverse events were evaluated throughout 52 weeks + additional 4 months for the patients with low B cell counts.
Outcome measures
| Measure |
Rituximab
n=19 Participants
All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.
Rituximab: Rituximab 1000mg IV on Days 0 and 15
|
|---|---|
|
Number of Participants Experiencing Serious and Non Serious Adverse Events
|
19 Participants
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: All patients enrolled in the study
Outcome measures scored as complete response(CR),partial(PR),and none(NR) at 24 weeks.For thrombocytopenia,CR defined as a platelet count of ≥150×109/μl,PR as 100-149,and NR as \<100.For CVD,CR defined as the disappearance of cardiac lesions,PR as 50%improvement,and NR as no change.For skin ulcer,CR defined as disappearance,PR as 50% improvement,and NR as no change.For aPL nephropathy,CR defined as a normal serum creatinine level,inactive urinary sediment,and urinary protein:creatinine 0.5;PR as a serum cr level 15%above baseline,RBCs per high-power field 50%above baseline with no casts,50%improvement in the urinary prt:cr,and estimated GFR 10%above baseline;and NR as the absence of C/PR.For cognitive dysfunction,CR defined as normalization of the cognitive impairment index with 50%improvement,PR as abnormal index with 50%,and NR as no change.
Outcome measures
| Measure |
Rituximab
n=19 Participants
All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.
Rituximab: Rituximab 1000mg IV on Days 0 and 15
|
|---|---|
|
The Efficacy of Rituximab
Complete Response
|
7 Participants
|
|
The Efficacy of Rituximab
Partial Response
|
4 Participants
|
|
The Efficacy of Rituximab
No Response
|
6 Participants
|
|
The Efficacy of Rituximab
Could not tolerate the infusion (not evaluated)
|
2 Participants
|
Adverse Events
Rituximab
Serious events: 12 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab
n=19 participants at risk
All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.
Rituximab: Rituximab 1000mg IV on Days 0 and 15
|
|---|---|
|
Nervous system disorders
Antiepileptic drug adjustment (history of seizure disorder)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Nervous system disorders
Brain surgery (history of seizure disorder)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Nervous system disorders
Subdural hematoma
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Nervous system disorders
New-onset focal motor seizure due to previous stroke
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Nervous system disorders
48-hour EEG monitoring and new-onset partial sensory seizure
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Pneumonia
|
10.5%
2/19 • Number of events 2 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Viral gastroenteritis/dehydration/cellulitis
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Vascular disorders
Recurrent deep vein thrombosis
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Vascular disorders
Post-phlebitic syndrome
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Cardiac disorders
Multifocal atrial tachycardia due to resolving pneumonia
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Immune system disorders
Allergy-Trimethoprim/sulfamethoxazole treatment
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
Other adverse events
| Measure |
Rituximab
n=19 participants at risk
All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.
Rituximab: Rituximab 1000mg IV on Days 0 and 15
|
|---|---|
|
Cardiac disorders
Chest pain with fever, chills, and low back pain
|
5.3%
1/19 • Number of events 2 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Cardiac disorders
Transient chest pressure
|
15.8%
3/19 • Number of events 3 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Skin and subcutaneous tissue disorders
Diffuse severe erythematous rash
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Skin and subcutaneous tissue disorders
Facial rash
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Cardiac disorders
Transient palpitations (recurrence)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Vascular disorders
Deep vein thrombosis (recurrence)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Vascular disorders
Raynaud's phenomenon (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Skin and subcutaneous tissue disorders
Rash (diffuse) within 1 week of rituximab infusion (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Skin and subcutaneous tissue disorders
Rash (local) within 1 week of rituximab infusion (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Skin and subcutaneous tissue disorders
Rash (local) due to nail glue allergy (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Gastrointestinal disorders
Gastrointestinal reflux disease (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Blood and lymphatic system disorders
Epistaxis (recurrence)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Upper respiratory tract infection
|
31.6%
6/19 • Number of events 6 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Tonsillitis, otitis, sinusitis
|
15.8%
3/19 • Number of events 3 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Urinary tract infection
|
15.8%
3/19 • Number of events 3 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Bronchitis
|
10.5%
2/19 • Number of events 2 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Acute gastroenteritis
|
10.5%
2/19 • Number of events 2 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Cellulitis
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Herpes zoster infection within 2 weeks of rituximab infusion (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Infections and infestations
Herpes zoster infection while noncompliant with prophylaxis (recurrence)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia (local) (new)
|
10.5%
2/19 • Number of events 2 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Musculoskeletal and connective tissue disorders
Arthritis (diffuse) within 1 week of the infusion (new)
|
10.5%
2/19 • Number of events 2 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia (diffuse) within 2 weeks of the infusion (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia (local) (recurrence)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Musculoskeletal and connective tissue disorders
Carpal tunnel syndrome (recurrence)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Musculoskeletal and connective tissue disorders
Gout flare (recurrence)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Musculoskeletal and connective tissue disorders
Shoulder dislocation (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Musculoskeletal and connective tissue disorders
Elbow incidental MRI metallic artifact finding (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Nervous system disorders
Seizures (history of partially controlled seizures) (recurrence)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Psychiatric disorders
Depression (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Nervous system disorders
Migraine (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
|
Nervous system disorders
Headache (severe, transient) (new)
|
5.3%
1/19 • Number of events 1 • 52 weeks
An adverse event (AE) was defined as any unfavorable medical occurrence, regardless of causality. A serious adverse event (SAE) was defined as an AE meeting ≥1 of the following criteria: death, life-threatening, requiring or prolonging inpatient hospitalization, disabling, or resulting in a congenital anomaly.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place