Table 18General characteristics of comparative studies on off-label rFVIIa use for intracranial hemorrhage

ArticleStudy DesignStudy Setting/Time PeriodSample Size and Dose, μg/kgPopulation CharacteristicsOutcomes Evaluated
Mean Age(SD) [Range]Inclusion/Exclusion CriteriaDirectIndirect
Mayer 2005a23RCT
Treatment
73 centers

Australia, Europe, Asia, North America

8/2002–3/2004
All Rx: 303
40: 108
80: 92
160: 103

Ucare: 96
Rx:
40: 67 (12)
80: 65 (12)
160: 64
(13)

Ucare:
68 (12)
Inclusion:
-spontaneous ICH
-treatment within 4 hrs of symptoms onset
-over 18 years old

Exclusion:
-deep coma (GCS 3–5)
-surgical hematoma evacuation planned within 24h
-secondary ICH (e.g. related to trauma)
-known oral anticoagulant use, history of coagulopathy, or thrombocytopenia
-any history of thrombotic disease*
-previous disability (mRS>2)
Mortality

Adverse events including TE events

Poor functional outcome (mRS 4–6)
Change in hematoma volume
Mayer 2005b86RCT

Treatment
14 centers

Australia, Europe, Asia

8/2001–10/2002
All Rx: 36
10: 6
20: 6
40: 6
80: 6
120: 6
160: 6

Ucare: 11
Rx:
10: 51 (9)
20: 68 (22)
40: 68 (16)
80: 58 (11)
120: 64
(14)
160: 53
(12)

Ucare:
66 (14)
Inclusion:
-spontaneous ICH
-treatment within 4 hrs of symptoms onset
-over 18 years old

Exclusion:
-deep coma (GCS 3–5)
-surgical hematoma evacuation planned within 24h
-secondary ICH (e.g. related to trauma)
-known oral anticoagulant use, history of coagulopathy, or thrombocytopenia
-any history of thrombotic disease
-previous disability (mRS>2)
Mortality

Adverse events including TE events

Poor functional outcome (mRS 4–6)
Mayer 200687RCT

Treatment
17 centers

USA

11/2001–3/2003
All Rx: 32
5: 8
20: 8
40: 8
80: 8

Ucare: 8
Rx:
5: 72 (10)
20: 60 (15)
40: 64 (13)
80: 62 (12)

Ucare:
67 (13)
Inclusion:
-spontaneous ICH
-treatment within 4 hrs of symptoms onset
-over 18 years old

Exclusion:
-deep coma (GCS 3–5)
-surgical hematoma evacuation planned within 24h
-secondary ICH (e.g. related to trauma)
-known oral anticoagulant use, history of coagulopathy, or thrombocytopenia
-any history of thrombotic disease
-previous disability (mRS>2)
Mortality

Adverse events including TE events

Poor functional outcome (mRS 4–6)
Change in hematoma volume
Mayer 200888RCT

Treatment
122 centers

Australia, Europe, Asia, North America

5/2005–2/2007
All Rx: 573
20: 276
80: 297

Ucare: 268
Rx:
20: 65 (14)
80: 65 (13)

Ucare:
65 (14)
Inclusion:
-spontaneous ICH
-treatment within 4 hrs of symptoms onset
-over 18 years old

Exclusion:
-deep coma (GCS 3–5)
-surgical hematoma evacuation planned within 24h
-secondary ICH (e.g. related to trauma)
-known oral anticoagulant use, history of coagulopathy, or thrombocytopenia
-known recent thrombotic disease (within 30 days of enrollment)
-previous disability (mRS>2)
Mortality

Adverse events including TE events

Poor functional outcome (mRS 5–6, but with extrapolation possible to mRS 4–6)
Change in hematoma volume
Ilyas 200889Retrospective

comparative Treatment
1 University hospital

USA

2/2000-NR
Rx: 24
Range 10–100

Ucare:30
Rx:
76.5 (11)

Ucare:
76.4 (12.4)
Inclusion:
-new or evolving intracranial hemorrhage (ICH or subdural hematoma)
-use of warfarin
-INR>1.4

Exclusion: NR
Mortality

Adverse events including TE events
Time to correction of INR
Pickard 200090Prospective comparative

Treatment
Multicenter

NR

NR
All Rx: 5
80: 2
80+3.5/h CI: 2
80+7.0/h CI: 1

UCare: 5
Rx: NR

UCare: NR
Inclusion:
-subarachnoid hemorrhage (grade I, II, or III on World Federation of Surgeons scale) confirmed on head CT or lumbar puncture

Exclusion: NR
Adverse events including TE eventsPET scan markers of cerebral blood flow and oxygen extraction
Brody 200591Retrospective comparative

Treatment
1 University hospital

USA

3/2002–1/2003
Rx: 12
Mean 4.8 mg SD
2.1 mg

UCare 15
Rx:
71 (13)

UCare: 77 (7)
Inclusion:
-spontaneous warfarin-associated ICH
-INR>1.3

Exclusion: NR
Mortality

Adverse events including TE events

Functional outcome (GCS)
ICU and hospital LOS
Hallevi 200892Retrospective comparative

Treatment
1 University hospital

USA

NR
All Rx: 46
40 (on warfarin):
NR
80 (not on warfarin): NR

UCare: 148
Rx:
60 [38–87]

UCare:
58 [40–80]
Inclusion:
-spontaneous ICH (could include those on warfarin)

Exclusion:
-GCS<5
-Recent thromboembolic event
Mortality

Adverse events including TE events

Functional outcome (mRS)
Change in hematoma volume

These studies did not meet inclusion criteria for detailed review in the comparative effectiveness analyses due to being poor quality (Table 14), but are included in the qualitative sensitivity discussions for this indication (in the section above, “Consideration of poor quality comparative observational studies”) and in the overall harms analyses near the end of this report;

*

Mayer 2005a23 excluded patients with symptomatic thrombotic or vaso-occlusive disease within 30 days of symptoms onset. This was amended midway through the trial to exclude patients with any history of thrombotic of vaso-occlusive disease;

Rx=treatment group(s); Ucare=usual care; GCS=Glasgow Coma Scale; mRS=modified Rankin Scale; CI=continuous infusion; ICU=intensive care unit; LOS=length of stay

From: Results

Cover of Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care [Internet].
Comparative Effectiveness Reviews, No. 21.
Yank V, Tuohy CV, Logan AC, et al.

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