Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials

Konark Malhotra, Jason J. Chang, Arjun Khunger, David Blacker, Jeffrey A Switzer, Nitin Goyal, Adrian V. Hernandez, Vinay Pasupuleti, Andrei V. Alexandrov, Georgios Tsivgoulis

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke. Methods: Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models. Results: We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0–2) (RR = 1.31; 95% CI 0.98–1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI − 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0–2 (RR = 1.59; 95% CI 1.19–2.12, p = 0.002; I2 = 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I2 = 47%), whereas reduced the 3-month NIHSS (MD − 2.84; 95% CI − 5.55, − 0.13; p = 0.04; I2 = 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion. Conclusions: Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.

Original languageEnglish (US)
Pages (from-to)1871-1879
Number of pages9
JournalJournal of Neurology
Volume265
Issue number8
DOIs
StatePublished - Aug 1 2018

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Minocycline
Meta-Analysis
Randomized Controlled Trials
Stroke
Therapeutics
Odds Ratio
Cerebral Hemorrhage
National Institutes of Health (U.S.)
Safety
Neuroprotective Agents
Neuroimaging
Myocardial Infarction
Placebos
Databases
Mortality

Keywords

  • Intracerebral hemorrhage
  • Ischemic stroke
  • Minocycline
  • Recovery

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Minocycline for acute stroke treatment : a systematic review and meta-analysis of randomized clinical trials. / Malhotra, Konark; Chang, Jason J.; Khunger, Arjun; Blacker, David; Switzer, Jeffrey A; Goyal, Nitin; Hernandez, Adrian V.; Pasupuleti, Vinay; Alexandrov, Andrei V.; Tsivgoulis, Georgios.

In: Journal of Neurology, Vol. 265, No. 8, 01.08.2018, p. 1871-1879.

Research output: Contribution to journalArticle

Malhotra, K, Chang, JJ, Khunger, A, Blacker, D, Switzer, JA, Goyal, N, Hernandez, AV, Pasupuleti, V, Alexandrov, AV & Tsivgoulis, G 2018, 'Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials', Journal of Neurology, vol. 265, no. 8, pp. 1871-1879. https://doi.org/10.1007/s00415-018-8935-3
Malhotra, Konark ; Chang, Jason J. ; Khunger, Arjun ; Blacker, David ; Switzer, Jeffrey A ; Goyal, Nitin ; Hernandez, Adrian V. ; Pasupuleti, Vinay ; Alexandrov, Andrei V. ; Tsivgoulis, Georgios. / Minocycline for acute stroke treatment : a systematic review and meta-analysis of randomized clinical trials. In: Journal of Neurology. 2018 ; Vol. 265, No. 8. pp. 1871-1879.
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abstract = "Background: Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke. Methods: Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models. Results: We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0–2) (RR = 1.31; 95{\%} CI 0.98–1.74, p = 0.06) and 3-month BI (MD = 6.92; 95{\%} CI − 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0–2 (RR = 1.59; 95{\%} CI 1.19–2.12, p = 0.002; I2 = 58{\%}) and 3-month BI (MD = 12.37; 95{\%} CI 5.60, 19.14, p = 0.0003; I2 = 47{\%}), whereas reduced the 3-month NIHSS (MD − 2.84; 95{\%} CI − 5.55, − 0.13; p = 0.04; I2 = 86{\%}). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion. Conclusions: Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.",
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AU - Malhotra, Konark

AU - Chang, Jason J.

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AU - Blacker, David

AU - Switzer, Jeffrey A

AU - Goyal, Nitin

AU - Hernandez, Adrian V.

AU - Pasupuleti, Vinay

AU - Alexandrov, Andrei V.

AU - Tsivgoulis, Georgios

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N2 - Background: Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke. Methods: Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models. Results: We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0–2) (RR = 1.31; 95% CI 0.98–1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI − 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0–2 (RR = 1.59; 95% CI 1.19–2.12, p = 0.002; I2 = 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I2 = 47%), whereas reduced the 3-month NIHSS (MD − 2.84; 95% CI − 5.55, − 0.13; p = 0.04; I2 = 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion. Conclusions: Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.

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