2025 LOCATE Trial Results

L-Oxiracetam for TBI Recovery: 2025 LOCATE Trial Results

Traumatic brain injury can leave people struggling with memory, attention, and daily thinking skills long after the initial trauma. In the 2025 LOCATE trial, a Phase 3 study of 590 patients, L-oxiracetam improved cognitive scores almost 9 points more than placebo at 90 days, a meaningful gain for mild to moderate TBI survivors.

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Phase 3 Clinical Trial • 590 Patients • 51 Hospitals
Quick Reference

Key Takeaways

Essential information about L-oxiracetam and its role in traumatic brain injury recovery

Question Answer
What is L-oxiracetam in traumatic brain injury? L-oxiracetam is the pure S-enantiomer of oxiracetam, a racetam nootropic. The 2025 LOCATE trial shows it can significantly improve cognitive recovery in mild to moderate TBI compared to placebo and racemic oxiracetam.
How large and rigorous was the main L-oxiracetam TBI study? The LOCATE trial enrolled 590 adults across 51 hospitals in China in a double-blind, randomized design, which is Level 1 clinical evidence and currently the strongest data set for oxiracetam-class drugs in TBI.
How much better was cognition with L-oxiracetam vs placebo? At 90 days, L-oxiracetam patients improved by 20.45 points on the LOTCA test versus 11.47 with placebo, a nearly 9-point difference that indicates moderate effect size and clinically relevant gains.
Is L-oxiracetam better than standard oxiracetam after TBI? Yes. L-oxiracetam outperformed the 6 g/day racemate on LOTCA with a 4.54-point advantage at 90 days, and showed fewer treatment-related adverse events, supporting the idea that the S-enantiomer is both more effective and better tolerated.
Which cognitive problems after TBI does L-oxiracetam help most? LOCATE reported benefits in visual and spatial perception, motor praxis, visuomotor organization, thinking operations, and domains related to attention and concentration, which are core deficits for many mild to moderate TBI patients.
How does L-oxiracetam fit within the broader nootropics landscape? Within the broader category of racetams and cognitive enhancers discussed in our overview of nootropics, L-oxiracetam stands out as one of the few with Phase 3 RCT data in a well-defined clinical population.
Where can readers learn more about related compounds? For mechanism and dosing context, see our detailed oxiracetam cognitive enhancement guide, which explains how the racemate works and how L-oxiracetam builds on that pharmacology.

This information is based on peer-reviewed clinical trial data

What is L-Oxiracetam?

Understanding L-Oxiracetam: From Racetam Nootropic to TBI Drug Candidate

L-oxiracetam is the S-enantiomer of oxiracetam, a synthetic racetam that has been studied for decades for memory and learning. Oxiracetam itself is a 2-pyrrolidone derivative known to modulate AMPA receptors and enhance acetylcholine signaling, which supports synaptic plasticity and cognitive processing.

In the context of traumatic brain injury, these mechanisms are attractive because TBI disrupts glutamatergic transmission, cholinergic tone, and neuronal energy metabolism. The LOCATE trial deliberately chose L-oxiracetam to test whether isolating the more active stereoisomer could amplify the benefits seen with standard oxiracetam while reducing side effects.

From a pharmacology standpoint, this is a classic example of moving from a racemate to a chiral-optimized molecule to target cognition more precisely.

AMPA Modulation

Enhances glutamatergic transmission for better synaptic plasticity

Cholinergic Support

Boosts acetylcholine signaling critical for memory and learning

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Clinical Evidence

The LOCATE Trial Design: How L-Oxiracetam Was Tested After Traumatic Brain Injury

A rigorous Phase 3 study that sets the gold standard for TBI research

Study Overview

The LOCATE trial is the pivotal study that put L-oxiracetam on the map for TBI. Conducted from 2019 to 2024 across 51 hospitals in China, it enrolled adults with mild to moderate traumatic brain injury, defined by a Glasgow Coma Scale (GCS) score of 10 to 15.

Treatment started within 72 hours of injury, which reflects a realistic acute-care window for hospital-managed TBI.

590
Total Patients
51
Hospital Sites
72h
Treatment Window
90d
Follow-up Period

Treatment Arms

L-oxiracetam 4 g/day
Pure S-enantiomer
n=235
Racemic oxiracetam 6 g/day
Standard formulation
n=236
Placebo
Control group
n=119

Multicenter, double-blind, placebo-controlled design — Neither participants nor clinicians knew which treatment was given

Primary Endpoint

Change in the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score at 90 days, chosen because it covers multiple cognitive domains relevant to TBI recovery including visual perception, spatial perception, motor praxis, visuomotor organization, thinking operations, attention, and concentration.

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Oxiracetam

Although its exact working mechanism remains unknown, Oxiracetam has been shown to provide powerful cognitive support:

AMPA Receptor Modulation
Positively modulates AMPA-sensitive glutamate receptors in neurons
Acetylcholine Release
Stimulates the release of acetylcholine in the brain
Neuroprotection
Inhibits pre-programmed cell apoptosis (death) in neurons
Cellular Energy Production
Stimulates production of cellular energy, such as glucose
Enhanced Receptor Density
Increases density of 1,4-dihydropyridine receptors in cerebral cortex
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Clinical Results

How Much Did L-Oxiracetam Improve Cognitive Outcomes After TBI?

The data shows statistically significant and clinically meaningful improvements in cognitive function

Primary Outcome at 90 Days

LOTCA Score Improvements

20.45
points improvement
from baseline
L-oxiracetam 4g/day
15.90
points improvement
from baseline
Oxiracetam 6g/day
11.47
points improvement
from baseline
Placebo
8.97
point advantage
vs Placebo (P < 0.001)
95% CI: 5.69 to 12.26
~0.48
effect size
Moderate & Substantial
Clinically meaningful improvement

MoCA Secondary Outcomes

Secondary outcomes, such as Montreal Cognitive Assessment (MoCA) scores, also improved at 90 days:

L-oxiracetam
MoCA improvement
+5.47
Placebo
MoCA improvement
+4.37

A smaller but statistically significant advantage that supports a broader cognitive benefit across multiple assessment tools.

Real-World Impact

These gains reflect better performance in daily cognitive tasks such as:

Processing visual information
Better recognition and interpretation
Orienting in space
Improved spatial awareness
Planning actions
Enhanced executive function
Coordinating eye-hand movements
Better motor coordination
Did You Know?

At 14 days, patients on L-oxiracetam improved their LOTCA scores by 13.76 points versus 7.45 with placebo, a 6.31-point advantage with P < 0.001, indicating that cognitive gains began as early as the second week after traumatic brain injury.

Molecular Advantage

L-Oxiracetam vs Racemic Oxiracetam: Why the S-Enantiomer Matters

A key strength of the LOCATE trial is that it directly compared L-oxiracetam to standard racemic oxiracetam rather than only to placebo. On the 90-day LOTCA change, L-oxiracetam had a least-squares mean advantage of 4.54 points over the 6 g/day racemate, with P < 0.001.

This suggests that the S-enantiomer is not just equivalent, but clinically superior for cognitive recovery after TBI.

From our perspective, this supports a broader trend in pharmacology: optimizing chiral molecules to capture the active stereoisomer and discard the less helpful or more side-effect-prone component.

L-oxiracetam
4 g/day
Superior Results
Lower dose, better outcomes, fewer side effects
Racemic Oxiracetam
6 g/day
Standard Results
Higher dose, moderate outcomes
Key Insight

LOCATE used 6 g/day of oxiracetam versus 4 g/day of L-oxiracetam, yet the lower total dose of the S-enantiomer still performed better, which is meaningful for future prescribing and product development.

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Historical Dosing Context

For racetams, the classic dosing for oxiracetam in cognitive studies ranges from 800 mg to 2,400 mg daily, usually split into two or three doses, as we outline in our oxiracetam guide.

Standard Oxiracetam
800-2,400 mg/day
Typical cognitive support dosing
LOCATE L-Oxiracetam
4,000 mg/day
Acute TBI treatment protocol
Cognitive Benefits

Which Cognitive Domains After TBI Improve With L-Oxiracetam?

The LOCATE trial measured specific cognitive functions to understand exactly where L-oxiracetam helps most

The LOCATE trial did not limit itself to a single global score. It broke down LOTCA and related tests into specific domains, which helps clinicians predict which patients might benefit most.

Visual Perception

Improved ability to recognize, interpret, and make sense of visual information in the environment

Spatial Perception

Enhanced understanding of spatial relationships, distances, and navigation in three-dimensional space

Motor Praxis

Better planning and execution of coordinated movements and skilled motor actions

Visuomotor Organization

Improved coordination between visual input and motor output for complex tasks

Thinking Operations

Enhanced executive functions including problem-solving, reasoning, and decision-making

Attention & Concentration

Better sustained focus, selective attention, and ability to concentrate on tasks

Real-World Patient Impact

What This Means for TBI Survivors

Common TBI Complaints

  • Trouble judging distances
  • Struggling with navigation
  • Clumsiness during fine motor tasks
  • Difficulty planning sequences
  • Mental fatigue when multitasking

L-Oxiracetam Benefits

  • Better spatial judgment
  • Improved orientation abilities
  • Enhanced motor coordination
  • Stronger executive function
  • Sustained attention capacity

The pattern of benefit suggests that L-oxiracetam is not only a memory enhancer but also a broad cognitive support that could interact favorably with occupational and physical therapy programs that target the same skills.

Safety Profile

Safety and Tolerability: Is L-Oxiracetam Safe for TBI Patients?

Safety is critical in TBI, where patients may already be on multiple medications and often have comorbid conditions

Overall Adverse Event Rates

In LOCATE, the overall incidence of any adverse event was similar across all three groups, indicating that adding either form of oxiracetam did not materially increase global adverse event rates compared to standard care plus placebo.

65.96%
L-oxiracetam
Any adverse event
66.53%
Oxiracetam
Any adverse event
67.23%
Placebo
Any adverse event

P = 0.980 — No statistically significant difference between groups

Key Safety Advantage

L-Oxiracetam Shows Superior Tolerability

Where L-oxiracetam distinguished itself was in treatment-related adverse events

9.36%
L-oxiracetam
Treatment-related AEs
Best Profile
17.37%
Oxiracetam
Treatment-related AEs
Higher Rate
9.24%
Placebo
Treatment-related AEs
Baseline

P = 0.049

Statistically significant advantage for L-oxiracetam

Discontinuation Rates

Adverse events leading to permanent discontinuation were significantly lower with L-oxiracetam:

L-oxiracetam
Discontinuation rate
0.43%
Oxiracetam
Discontinuation rate
3.81%
Placebo
Discontinuation rate
5.88%

P = 0.004 — Highly significant difference favoring L-oxiracetam

Clinical Implications

For frontline clinicians this suggests that L-oxiracetam offers a better tolerability balance than the racemate in a hospital setting.

Key Takeaway

L-oxiracetam provides the cognitive benefits of oxiracetam therapy while maintaining a safety profile comparable to placebo and superior to the racemic formulation.

  • Fewer treatment-related side effects
  • Lower discontinuation rates
  • Better patient compliance potential
  • Suitable for complex medication regimens
Did You Know?

Treatment-related adverse events occurred in 9.36% of L-oxiracetam patients compared with 17.37% on racemic oxiracetam, while remaining on par with placebo at 9.24%, highlighting L-oxiracetam's favorable tolerability profile in traumatic brain injury care.

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Important Context

Functional Recovery vs Cognitive Recovery: What L-Oxiracetam Does and Does Not Change

An important nuance in the LOCATE data is that while cognitive scores improved clearly with L-oxiracetam, global functional outcomes, as measured by the Glasgow Outcome Scale Extended (GOSE), did not significantly differ between groups.

Good Recovery Rates at 90 Days (GOSE 7-8)

97.43%
L-oxiracetam
97.31%
Oxiracetam
98.92%
Placebo

P = 0.667 (No significant difference)

We interpret this to mean that L-oxiracetam is best viewed as a cognitive enhancer within a comprehensive rehabilitation program, not a stand-alone solution that will determine whether a patient returns to work or independence.

Cognitive Enhancement
Sharpens cognitive tools like memory, attention, and processing
Holistic Recovery
Physical limitations, mood disorders, and social factors also shape outcomes
Integrated Approach
Best results come from combining pharmacologic and therapeutic interventions
Setting Realistic Expectations

For clinicians and families, understanding these distinctions can prevent overpromising and support realistic treatment planning. L-oxiracetam enhances cognition but doesn't replace comprehensive rehabilitation.

Broader Context

How L-Oxiracetam Fits Into the Broader Nootropic and TBI Landscape

Understanding where L-oxiracetam stands among cognitive enhancement compounds and TBI interventions

L-Oxiracetam

Stands out because it now has large-scale, Phase 3 randomized controlled data in a specific clinical population.

  • 590 patients across 51 hospitals
  • Double-blind, placebo-controlled design
  • Level 1 clinical evidence for TBI
  • Well-defined patient population (GCS 10-15)

Many Other Nootropics

Supported by small, heterogeneous studies or preclinical work with less rigorous TBI-focused evidence.

  • Noopept — promising mechanisms, limited TBI data
  • Bromantane — interesting preclinical work
  • FLModafinil — primarily for healthy users
  • Various compounds — awaiting rigorous TBI trials

Complementary Approaches

Natural and nutraceutical strategies for brain trauma recovery

Natural Support

Reviews of nutraceutical interventions highlight anti-inflammatory and HPA-axis modulating agents

Mental Health Support

Resources on mood, anxiety, and focus support discuss lifestyle and targeted nutrients

Anti-Inflammatory

Addressing neuroinflammation through diet, supplements, and lifestyle modifications

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Cognitive aging prevention strategies

Our Perspective

We see L-oxiracetam as complementary to these approaches, specifically targeting post-TBI cognitive domains while other interventions support emotional regulation and neuroinflammation.

L-oxiracetam addresses the cognitive side of recovery with robust clinical evidence, while natural approaches support the broader healing process through multiple complementary mechanisms.

Clinical Application

Clinical Dosing, Timing, and Practical Considerations After TBI

Understanding how L-oxiracetam was administered in LOCATE and what it means for clinical practice

LOCATE Trial Protocol

Daily Dose

4 g/day

L-oxiracetam

Treatment Window

≤72 hours

From time of injury

Administration

Intravenous initially

Transitioned according to protocol

Standard Outpatient Oxiracetam

Daily Dose Range

800-2,400 mg

Racemic oxiracetam for cognitive support

Dosing Schedule

2-3 times daily

Divided doses throughout the day

Administration Route

Oral tablets/powder

For longer-term cognitive support

Key Difference

This higher, acute-phase dosing is distinct from typical outpatient oxiracetam protocols. For TBI, the goal is to intervene early in the window where secondary injury processes and maladaptive plasticity are active.

LOCATE TBI Protocol
4,000 mg/day IV, acute phase
Standard Cognitive Support
800-2,400 mg/day oral, chronic use

For Clinicians Considering Translation Into Practice

Three critical points for implementing L-oxiracetam therapy in TBI care

1

Start Early

Begin treatment when feasible within the acute window to maximize neuroprotective benefits

2

Match Protocol

Follow IV loading and oral maintenance paradigm as closely as local regulations allow

3

Integrate Therapy

Combine pharmacologic treatment with structured cognitive rehabilitation programs

For Patients and Families

It is important to understand that L-oxiracetam in LOCATE was a prescription-style hospital therapy, not a casual supplement, and it was used under close monitoring and standardized protocols. Always consult with neurologists or rehabilitation specialists familiar with TBI pharmacology.

Important Limitations

Limitations of the Current Evidence and What Comes Next for L-Oxiracetam in TBI

Despite its strengths, LOCATE has limitations that we discuss openly when advising readers

Patient Population

Focused on mild to moderate TBI (GCS 10-15). Cannot automatically generalize to severe TBI, pediatric patients, or chronic post-concussive syndrome.

Geographic Scope

Conducted entirely in China across 51 hospitals. May limit extrapolation to different healthcare systems or demographic profiles until replicated elsewhere.

Follow-Up Period

90-day endpoint is reasonable but longer-term data would clarify whether cognitive advantages persist, widen, or diminish over time.

Combination Studies

Future studies might explore combinations with intensive cognitive rehabilitation or compare L-oxiracetam to other neuroprotective agents.

Pediatric Data

No data on children and adolescents with TBI. Safety and efficacy in younger populations remains to be established.

Severe TBI

Excluded patients with GCS < 10. Effect in severe traumatic brain injury cases needs separate investigation.

Balanced Scientific Perspective

Nonetheless, within its defined scope, LOCATE provides high-quality evidence that the S-enantiomer is both effective and safe in early TBI recovery.

What We Know

  • Level 1 evidence in mild-moderate TBI
  • Clinically significant cognitive improvement
  • Superior to racemic oxiracetam
  • Excellent safety profile

What We Need

  • Data in severe TBI populations
  • Pediatric safety and efficacy studies
  • Long-term outcome data (>90 days)
  • Replication in Western populations
Future Research

What Comes Next?

Expanded Populations

Studies in severe TBI, pediatric patients, chronic post-concussive syndrome, and diverse geographic populations

Combination Therapies

L-oxiracetam paired with intensive cognitive rehabilitation or other neuroprotective agents

Long-Term Outcomes

6-month, 1-year, and longer follow-up to understand durability of cognitive benefits

Mechanistic Studies

Deeper understanding of how L-oxiracetam modulates recovery pathways at cellular and molecular levels

Summary & Recommendations

Conclusion

Key Conclusion

For traumatic brain injury, L-oxiracetam is one of the few nootropic-class compounds supported by large, modern Phase 3 data in a well-defined patient population. In the LOCATE trial, it delivered almost a 9-point advantage over placebo on LOTCA at 90 days, outperformed racemic oxiracetam by 4.54 points, and did so with a safety profile comparable to placebo and better than the racemate for treatment-related adverse events.

These findings make a strong case for developing L-oxiracetam as a clinical standard in early post-TBI cognitive rehabilitation.

As a team focused on evidence-based cognitive support, we view L-oxiracetam not as a magic bullet, but as a meaningful, data-driven tool to pair with comprehensive rehab, psychological care, and, where appropriate, nutraceutical strategies.

Evidence Quality

  • 590 patients across 51 hospitals
  • Double-blind, placebo-controlled
  • Level 1 clinical evidence
  • Statistically significant results

Clinical Benefits

  • 8.97-point LOTCA advantage vs placebo
  • 4.54-point advantage vs oxiracetam
  • Multiple cognitive domains improved
  • Excellent safety & tolerability

Recommendations for Implementation

For Clinicians

Work with neurologists or rehabilitation specialists familiar with TBI pharmacology. Begin treatment within the acute window studied in LOCATE (≤72 hours) when possible, and integrate with comprehensive rehabilitation programs.

For Patients & Families

Understand that L-oxiracetam is a prescription-style hospital therapy used under close monitoring. Benefits are most robust when treatment begins in the acute window and is combined with occupational therapy, physical rehabilitation, and psychological support.

Integrated Care Approach

With careful integration, L-oxiracetam offers a promising route to better cognitive outcomes after traumatic brain injury when combined with comprehensive medical care, therapy programs, and evidence-based lifestyle interventions.

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