Efficacy and safety of minocycline in the treatment of intracerebral haemorrhage: study design and protocol for a multicentre, randomised, open-label, blinded endpoint clinical trial.
Qu Y, Guo Z, et al. • European stroke journal • 2026
The ENHANCE trial is designed to evaluate the effectiveness and safety of minocycline in the treatment of intracerebral haemorrhage (ICH) through a prospective, multicentre, randomised, open-label, blinded-endpoint clinical trial.
Key Findings
Methods
The ENHANCE trial is an ongoing prospective, multicentre, randomised, open-label, blinded-endpoint clinical trial assessing minocycline for ICH treatment.
Trial is registered under Chinese Clinical Trials Registry identifier ChiCTR2500114607
Study design is described as PROBE (Prospective Randomised Open-label Blinded Endpoint)
The trial is multicentre in nature, suggesting enrolment across multiple hospital sites in China
The paper describes this as a study design and protocol publication, not a results paper
Methods
A total of 1248 patients with ICH within 24 hours of onset will be randomly assigned to minocycline or control groups at a 1:1 ratio.
624 patients will be assigned to the minocycline group and 624 to the control group
Patients must be enrolled within 24 hours of ICH onset
Randomisation ratio is 1:1 between treatment and control arms
The sample size of 1248 was presumably calculated to provide adequate statistical power for the primary endpoint
Methods
The minocycline dosing regimen consists of an initial 200 mg dose followed by 100 mg orally every 12 hours for 7 days, totalling 14 administrations.
Initial loading dose is 200 mg minocycline hydrochloride capsules
Maintenance dose is 100 mg orally every 12 hours
Treatment duration is 7 days
Total number of administrations is 14
The minocycline group receives this regimen in addition to guideline-based standard treatment
Methods
The control group receives only guideline-based standard treatment without minocycline.
No placebo is administered to the control group, consistent with the open-label design
Both groups receive the same underlying guideline-based treatment as the foundation of care
The open-label design means neither patients nor clinicians are blinded to treatment allocation
Endpoint assessment is blinded despite the open-label treatment allocation
Methods
The primary efficacy outcome is the proportion of patients with good functional outcomes, defined as a modified Rankin Scale (mRS) score of 0-2, at 180 days.
Good functional outcome is defined as mRS score of 0-2
The primary endpoint is assessed at 180 days (approximately 6 months) post-ICH
The mRS is a standard outcome measure widely used in stroke clinical trials
Endpoint evaluation is blinded to treatment allocation
Methods
Safety outcome measures include all adverse events and severe adverse events occurring during the study period.
Both adverse events (AEs) and severe adverse events (SAEs) are captured as safety endpoints
Safety monitoring covers the entire study period
Minocycline is described as a 'multi-target neuroprotective drug' with unclear benefit specifically in ICH
The safety profile of minocycline in the ICH population is one of the key unknowns the trial aims to address
Background
Minocycline is characterised as a multi-target neuroprotective drug whose potential benefit in ICH patients remains unclear prior to this trial.
The authors describe minocycline as a 'multi-target neuroprotective drug'
No definitive evidence of benefit in ICH existed at the time of trial design
The ENHANCE trial is positioned as the study designed to clarify this uncertainty
The rationale implies prior preclinical or mechanistic evidence supporting neuroprotection without conclusive clinical trial data in ICH
What This Means
This paper describes the design and protocol of a clinical trial called ENHANCE, which is testing whether minocycline — an antibiotic also known to have brain-protective properties — can improve outcomes for people who have suffered a brain bleed (intracerebral haemorrhage, or ICH). ICH is a severe form of stroke where bleeding occurs within the brain tissue itself, and currently there are very few proven drug treatments beyond supportive care. Minocycline has shown promise in laboratory and animal studies as a drug that can reduce brain injury through multiple mechanisms, but whether it actually helps human ICH patients has not been established.
The trial plans to enrol 1,248 ICH patients across multiple hospitals in China within 24 hours of their stroke. Half will receive minocycline (starting with a 200 mg dose, then 100 mg twice daily for 7 days) on top of standard care, while the other half receive standard care alone. The main question the trial asks is: at 6 months after the stroke, what proportion of patients in each group have recovered well enough to be largely independent (measured by a standard disability scale called the modified Rankin Scale). The trial also carefully tracks side effects and safety events throughout the study period.
This research suggests that if minocycline proves effective and safe in this large trial, it could represent one of the first drug treatments to meaningfully improve recovery after brain bleeds. The trial's rigorous design — with blinded outcome assessment despite open-label treatment — is intended to provide high-quality evidence. Results, once available, could have significant implications for how ICH is managed, given the current scarcity of effective pharmacological options for this devastating condition.
Qu Y, Guo Z, Qi S, Abuduxukuer R, Zhang P, Li H, et al.. (2026). Efficacy and safety of minocycline in the treatment of intracerebral haemorrhage: study design and protocol for a multicentre, randomised, open-label, blinded endpoint clinical trial.. European stroke journal. https://doi.org/10.1093/esj/aakag084