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Table 12.39 Effects of Progesterone in ABI

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Author Year   Country   Research Design   PEDro   Sample Size Methods Outcomes

Soltani et al. (2017) Iran

RCT

PEDro=7

N=48

Population: Experimental Group (n=20): Mean age=27.85yr; Mean GCS=7.7. Control Group (n=24): Mean Age=30.37yr; Mean GCS=7.7.

Intervention: 1 mg/kg of Progesterone was given intramuscularly every 12 hours for 5 days to the experimental group, while the control group received no treatment. Participants received treatment within 12 hours of initial trauma.

Outcome Measure: Glasgow Outcome Scale-Extended (GOS-E), Functional Independence Measure (FIM), serum progesterone levels, mortality.

1.        There were no significant differences between groups at 3 mo post-trauma based on treatment. However, at 6 mo post-trauma the progesterone group had significantly higher GOS-E scores (p=0.03), with only 1 death in the progesterone group compared to 7 in the control group.

 

2.        FIM scores showed a similar trend with no significant difference between groups at 3 mo but 6 mo post-trauma the progesterone group had significantly higher FIM scores (p<0.05).

3.        At baseline there was no significant difference between groups in terms of serum progesterone levels, however after the initiation of treatment the progesterone group maintained significantly higher progesterone levels until the end of the trial (p<0.05).

4.        The control group experienced significantly higher mortality compared to the progesterone group (p<0.05).

Skolnick et al.

 (2014a)

Belgium

RCT

PEDro=7

N=1195

Population: TBI; Progesterone (n=591): Median Age=35 yr; Gender: Male=464, Female=127; Median Time Post Injury=7 hr 4 min; GCS Range≤8. Placebo (n=588): Median Age=34 yr; Gender: Male=463, Female=125; Median Time Post Injury=7 hr 2 min; GCS≤8.

Intervention: Participants were randomized to receive either progesterone (0.71 mg/kg/hr loading dose, followed by a continuous maintenance infusion of 0.5 mg/kg/hr) or placebo for 120 hr. Outcomes were assessed at baseline and 6mo.

Outcome Measures: Glasgow Outcome Scale (GOS).

1.         There was no significant difference in the GOS scores of patients with the worst prognosis between groups (n=393; p=0.36).

2.         There was no significant difference in the GOS scores of patients with intermediate prognosis between groups (n=394; p=0.82).

3.         There was no significant difference in the GOS scores of patients with the best prognosis between groups (n=392; p=0.38).

Wright et al.

(2014)

USA

RCT

PEDro=10

N=882

Population: TBI; Median Age=35 yr; Gender: Male=650, Female=232; Mean Time Post Injury=218.1 min; Severity: Moderate=254, Moderate to Severe=472, Severe=156.

Intervention: Participants were randomized to receive one of intravenous infusions of progesterone (n=442) or placebo (n=440). Progesterone was administered continuously at 14.3 mL/hr for 1 hr, then at 10 mL/hr for 71 hr. The dose was tapered by 2.5 mL/hr every 8hr, for total treatment duration of 96hr. Outcomes were assessed at 6mo.

Outcome Measures: Glasgow Outcome Scale Extended (GOSE), Mortality, Adverse Effects.

1.        Favourable outcomes occurred in 51% of patients treated with progesterone and in 55.5% of the placebo group. Relative benefit was 0.95, meaning fewer favourable outcomes are expected in the progesterone group (RR: 0.95).

2.        Mortality at 6mo did not differ significantly between the two groups.

3.        The frequency of adverse effects did not differ significantly between the two groups, with the exception of phlebitis or thrombophlebitis, which was higher in the progesterone group (17.2% versus. 5.7%; relative risk, 3.03).

Shakeri et al.

 (2013)

Iran

RCT

PEDro=7

N=76

Population: TBI; Gender: Male=76, Female=0; Time Post Injury≤6 hr. Progesterone Group (n=38): Mean Age=33.97 yr; Mean GCS=5.74. Control Group (n=38): Mean Age=34.68 yr; Mean GCS=5.79.

Intervention: Participants were randomized to receive either progesterone (1 mg/kg every 12 hr for 3 days) or no treatment (control). Outcomes were assessed at 3mo.

Outcome Measures: Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS).

               

1.        Admission and discharge GCS were not significantly different between groups.

2.        GOS scores at 3 mo follow-up showed no significant differences between groups in terms of favourable outcomes.

3.        In patients with GCS=5-8, there was a significant difference in favourable outcomes between treatment and controls (16.67% versus 10%, p=0.03); this was not seen in patients with GCS<5.

Xiao et al.

(2008)

China

RCT

PEDro=7

N=159

Population: TBI; Progesterone (n=82): Mean Age=30 yr; Gender: Male=58, Female=24; Mean Time Post Injury=3.80 hr; Mean GCS=6.0. Placebo (n=77): Mean Age=31 yr; Gender: Male=57, Female=25; Mean Time Post Injury=3.65 hr; Mean GCS=6.1.

Intervention: Patients were randomized to receive intramuscular progesterone or placebo. Progesterone was administered at 1.0 mg/kg twice a day for 5 days.

Outcome Measures: Intracranial Pressure (ICP), Glasgow Outcome Scale (GOS), Modified Functional Independence Measure (mFIM), Mortality.

1.        Progesterone group showed more favourable outcomes on the GOS than controls at 3 mo (47% versus 31%, p=0.034) and 6 mo (58% versus 42%, p=0.048).

2.        Progesterone group had higher mean mFIM scores at 3 mo (8.02 versus 7.35, p<0.05) and 6 mo (9.87 versus 8.95, p<0.01).

3.        Mortality at 6 mo was significantly lower in the treatment group than the control group (18% versus 32%, p<0.039).

4.        No significant difference in ICP was noted between groups.

5.        No AEs were reported after treatment of progesterone.

Wright et al.

(2007)

USA

RCT

PEDro=10

N=100

Population: TBI; Mean Age=35.8yr; Gender: Male=71, Female=29; Mean Time Post Injury=379.2min; Severity: Mild/Moderate=28, Severe=72.

Intervention: Patients were randomized in a 4:1 ratio to intravenous progesterone (n=77) or placebo (n=23). Progesterone was administered at a leading dose of 0.71 mg/kg at 14 mL/hr for 1 hr, then at 10 mL/hr for 11 hr, followed by five 12 hr maintenance infusions at 10 mL/hr over 3 days. Outcomes were assessed 30 days post injury.

Outcome Measures: Glasgow Outcome Scale Extended (GOSE), Disability Rating Scale (DRS), Adverse Events (AE), Intracranial Pressure (ICP).

1.        AE rates and physiological variables (e.g. ICP) were similar between groups. No serious AEs were associated with progesterone.

2.        The placebo group had a higher 30 days mortality rate compared to the progesterone group (RR 0.43).

 

3.        Patients with severe injury (GCS=4-8) were functioning at a relatively poor level, regardless of group.

4.        For patients with moderate injury (GCS 9-12), those in the progesterone group were more likely to have moderate or good recovery on GOSE (55.6% versus 0%, p=0.0202) and better score on DRS (5.0 versus 12.7) when compared to the placebo group.