Scolaris Content Display Scolaris Content Display

Study flow diagram.
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Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Efficacy and safety for acute stroke, Outcome 1 Death or dependency.
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Analysis 1.1

Comparison 1 Efficacy and safety for acute stroke, Outcome 1 Death or dependency.

Comparison 1 Efficacy and safety for acute stroke, Outcome 2 Somnolence.
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Analysis 1.2

Comparison 1 Efficacy and safety for acute stroke, Outcome 2 Somnolence.

Comparison 1 Efficacy and safety for acute stroke, Outcome 3 Rhinitis.
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Analysis 1.3

Comparison 1 Efficacy and safety for acute stroke, Outcome 3 Rhinitis.

Comparison 1 Efficacy and safety for acute stroke, Outcome 4 Functional independence.
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Analysis 1.4

Comparison 1 Efficacy and safety for acute stroke, Outcome 4 Functional independence.

Comparison 2 Efficacy for acute ischemic stroke, Outcome 1 Death or dependency.
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Analysis 2.1

Comparison 2 Efficacy for acute ischemic stroke, Outcome 1 Death or dependency.

Comparison 2 Efficacy for acute ischemic stroke, Outcome 2 Functional independence.
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Analysis 2.2

Comparison 2 Efficacy for acute ischemic stroke, Outcome 2 Functional independence.

Comparison 3 Efficacy for acute hemorrhagic stroke, Outcome 1 Death or dependency.
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Analysis 3.1

Comparison 3 Efficacy for acute hemorrhagic stroke, Outcome 1 Death or dependency.

Comparison 3 Efficacy for acute hemorrhagic stroke, Outcome 2 Functional independence.
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Analysis 3.2

Comparison 3 Efficacy for acute hemorrhagic stroke, Outcome 2 Functional independence.

Comparison 4 Efficacy for TACS, Outcome 1 Functional independence.
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Analysis 4.1

Comparison 4 Efficacy for TACS, Outcome 1 Functional independence.

Comparison 5 Efficacy for early‐treated acute stroke, Outcome 1 Functional independence.
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Analysis 5.1

Comparison 5 Efficacy for early‐treated acute stroke, Outcome 1 Functional independence.

Summary of findings for the main comparison. Chlormethiazole compared with placebo for acute stroke

Chlormethiazole compared with placebo for acute stroke

Patient or population: people with acute stroke

Settings: inpatients

Intervention: chlormethiazole

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Chlormethiazole

Death or dependency

475 per 1000

487 per 1000

RR 1.03 (0.96 to 1.11)

2909 (4)

⊕⊕⊕⊝
Moderate1

Adverse events

Somnolence 113 per 1000

Rhinitis 25 per 1000

Somnolence 517 per 1000

Rhinitis 130 per 1000

RR 4.56 (3.50 to 5.95)

RR 4.75 (2.67 to 8.46)

2527 (2)

⊕⊕⊕⊝
Moderate1

Functional independence

525 per 1000

513 per 1000

RR 0.98 (0.92 to 1.05)

2909 (4)

⊕⊕⊕⊝
Moderate1

Other stroke scales

NIHSS

1367 (2)

SSS

2727 (3)

⊕⊕⊕⊝
Moderate1

In Lyden 2000, the mean change of the NIHSS score was ‐4.5 in the chlormethiazole group (N = 96) and ‐4.0 in the placebo group (N = 102; P = 0.36). In Lyden 2002, the change of NIHSS score (median (quartiles)) was ‐5.5 (‐11, 17) in the chlormethiazole group (N = 586) and ‐6.0 (‐10, 16) in the placebo group (N = 583; P = 0.68).

In Wahlgren 1999, no significant difference was found between the placebo and chlormethiazole groups for the change in score in the SSS 48‐point (P = 0.56) and SSS motor power score (P = 0.96). In Lyden 2000 and Lyden 2002, the change in score in the SSS was not significant in the two groups (P = 0.06 and P = 0.23, respectively).

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence Interval; NIHSS: National Institutes of Health Stroke Scale; RR: Risk Ratio; SSS: Scandinavian Stroke Scale

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Downgraded one level due to unclear risk of selection bias

Functional independence, defined as a BI score higher than 60 or a mRS score less than 3

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Summary of findings for the main comparison. Chlormethiazole compared with placebo for acute stroke
Summary of findings 2. Diazepam compared with placebo for acute stroke

Diazepam compared with placebo for acute stroke

Patient or population: people with acute stroke

Settings: inpatients

Intervention: diazepam

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Diazepam

Death or dependency

513 per 1000

481 per 1000

RR 0.94 (0.82 to 1.07)

849 (1)

⊕⊕⊕⊝
Moderate1

Adverse events

357 per 1000

355 per 1000

RR 0.99 (0.75 to 1.31)

865 (1)

⊕⊕⊕⊝
Moderate1

Functional independence

487 per 1000

519 per 1000

RR 1.07 (0.93 to 1.22)

849 (1)

⊕⊕⊕⊝
Moderate1

Other stroke scales

Not reported

Not reported

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Downgraded one level: one study with small sample size

Functional independence, defined as a BI score higher than 60 or a mRS score less than 3

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Summary of findings 2. Diazepam compared with placebo for acute stroke
Comparison 1. Efficacy and safety for acute stroke

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death or dependency Show forest plot

5

3758

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.95, 1.08]

1.1 Chlormethiazole versus placebo

4

2909

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.96, 1.11]

1.2 Diazepam versus placebo

1

849

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.82, 1.07]

2 Somnolence Show forest plot

2

2527

Risk Ratio (M‐H, Random, 95% CI)

4.56 [3.50, 5.95]

2.1 Chlormethiazole versus placebo

2

2527

Risk Ratio (M‐H, Random, 95% CI)

4.56 [3.50, 5.95]

3 Rhinitis Show forest plot

2

2527

Risk Ratio (M‐H, Random, 95% CI)

4.75 [2.67, 8.46]

3.1 Chlormethiazole versus placebo

2

2527

Risk Ratio (M‐H, Random, 95% CI)

4.75 [2.67, 8.46]

4 Functional independence Show forest plot

5

3758

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.94, 1.06]

4.1 Chlormethiazole versus placebo

4

2909

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.92, 1.05]

4.2 Diazepam versus placebo

1

849

Risk Ratio (M‐H, Random, 95% CI)

1.07 [0.93, 1.22]

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Comparison 1. Efficacy and safety for acute stroke
Comparison 2. Efficacy for acute ischemic stroke

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death or dependency Show forest plot

3

2646

Risk Ratio (M‐H, Random, 95% CI)

1.04 [0.96, 1.12]

1.1 Chlormethiazole versus placebo

3

2646

Risk Ratio (M‐H, Random, 95% CI)

1.04 [0.96, 1.12]

2 Functional independence Show forest plot

4

3394

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.93, 1.08]

2.1 Chlormethiazole versus placebo

3

2646

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.91, 1.05]

2.2 Diazepam versus placebo

1

748

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.96, 1.27]

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Comparison 2. Efficacy for acute ischemic stroke
Comparison 3. Efficacy for acute hemorrhagic stroke

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death or dependency Show forest plot

2

292

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.75, 1.30]

1.1 Chlormethiazole versus placebo

2

292

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.75, 1.30]

2 Functional independence Show forest plot

3

387

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.81, 1.16]

2.1 Chlormethiazole versus placebo

2

292

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.83, 1.21]

2.2 Diazepam versus placebo

1

95

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.50, 1.27]

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Comparison 3. Efficacy for acute hemorrhagic stroke
Comparison 4. Efficacy for TACS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Functional independence Show forest plot

2

635

Risk Ratio (M‐H, Random, 95% CI)

1.33 [1.08, 1.63]

1.1 Chlormethiazole versus placebo

2

635

Risk Ratio (M‐H, Random, 95% CI)

1.33 [1.08, 1.63]

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Comparison 4. Efficacy for TACS
Comparison 5. Efficacy for early‐treated acute stroke

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Functional independence Show forest plot

3

1314

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.80, 1.21]

1.1 Chlormethiazole versus placebo (< 6 hours)

2

1182

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.73, 1.19]

1.2 Diazepam versus placebo (< 3 hours)

1

132

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.85, 1.74]

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Comparison 5. Efficacy for early‐treated acute stroke