PDF: ULTRA
(2020)Objective
To determine whether ultra-early tranexamic acid (TXA) administration reduces hematoma expansion and improves outcomes in patients with spontaneous intracerebral hemorrhage (ICH).
Study Summary
Intervention
Multicenter, randomized, double-blind, placebo-controlled trial of IV tranexamic acid (1 g over 10 minutes followed by 1 g over 8 hours) vs. placebo in patients with spontaneous ICH presenting within 2 hours of symptom onset.
Inclusion Criteria
Adults with spontaneous supratentorial ICH confirmed by CT, GCS ≥ 8, symptom onset within 2 hours, and no planned surgical evacuation or contraindications to TXA.
Study Design
Arms: IV tranexamic acid vs. placebo (both with standard supportive care).
Patients per Arm: TXA: 460, Placebo: 460 (total N=920)
Outcome
Bottom Line
The ULTRA trial is designed to investigate if ultraearly and short-term (≤24h) tranexamic acid treatment in aneurysmal SAH patients improves clinical outcome at 6 months by reducing recurrent bleeding without increasing delayed cerebral ischemia. The detailed statistical analysis plan outlines the primary outcome of good functional status (mRS 0-3) and various secondary and safety outcomes.
Major Points
- Recurrent bleeding from an intracranial aneurysm after SAH is associated with unfavorable outcome and occurs in up to one in five patients, most often within the first 6 hours after the primary hemorrhage.
- Tranexamic acid (TXA) reduces the risk of recurrent bleeding, and administering it for a short duration (<24 hours) may not increase the risk of delayed cerebral ischemia (DCI).
- The ULTRA trial is a multicenter, prospective, randomized, open, blinded endpoint, parallel-group trial enrolling patients in the Netherlands.
- Participants are randomized 1:1 to standard care or to receive TXA at a loading dose of 1 g, immediately followed by 1 g every 8 hours for a maximum of 24 hours, in addition to standard care, as soon as SAH is diagnosed.
- TXA administration is stopped immediately prior to aneurysm treatment (coil or clip).
- The primary outcome is the modified Rankin Scale (mRS) score at 6 months after SAH, dichotomized into good (mRS 0-3) and poor (mRS 4-6) outcomes, assessed blind to treatment allocation.
- The study aims to increase the proportion of patients with a good outcome from 69% (standard care) to 77.1% (TXA), requiring a total sample size of 950 patients.
- Safety outcomes include recurrent bleeding, DCI, hydrocephalus, per-procedural complications, and other complications such as infections.
Study Design
- Study Type
- Multicenter, prospective, randomized, open-label, blinded-endpoint, parallel-group trial (Phase III)
- Randomization
- Yes
- Blinding
- Blinded outcome assessment (research nurse blinded to treatment allocation for mRS score).
- Sample Size
- 950
- Follow-up
- 6 months
- Centers
- 8 tertiary care centers and 16 referral centers
- Countries
- Netherlands
Primary Outcome
Definition: Clinical outcome at 6 months measured with the modified Rankin Scale (mRS) score, dichotomized into good (mRS 0-3) and poor (mRS 4-6) outcomes, assessed blind to treatment allocation.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| XX (XX%) (proportion good outcome) | XX (XX%) (proportion good outcome) | - (XX-XX) | - |
Limitations & Criticisms
- The study protocol describes the statistical analysis plan (SAP) rather than presenting trial results, so actual criticisms of the trial's findings are not available yet.
- The use of an open-label design for TXA administration may modulate possible treatment effects and introduce bias, although outcome assessment is blinded[cite: 3461].
- The informed consent procedure is delayed due to emergency circumstances, which is common in SAH trials but might impact patient autonomy[cite: 3430].
Citation
Post et al. Trials (2020) 21:199. https://doi.org/10.1186/s13063-020-4118-5