A randomized placebo-controlled trial of progesterone with or without hypothermia in patients with acute severe traumatic brain injury

OBJECTIVE: Among newer neuroprotectant modalities, hypothermia and progesterone have shown a beneficial role in preliminary studies enrolling patients with severe traumatic brain injury (sTBI). The primary objective of this study was to evaluate the efficacy of progesterone with or without prophylactic hypothermia in acute sTBI patients.

MATERIALS AND METHODS: This is a prospective, outcome assessor, statistician blinded, randomized, and placebo-controlled phase II trial of progesterone with or without hypothermia (factorial design). All adult patients (18-65 years) with acute sTBI (Glasgow coma score of 4-8) and presenting to trauma center within 8 h after injury were included in the trial. Computer-generated randomization was done after exclusion; sequentially numbered, opaque, sealed envelope technique was used for allocation concealment. The enrollment duration was from January 2012 to October 2014. The primary endpoint was dichotomized Glasgow outcome score (GOS) [poor recovery = GOS 1-3; good recovery = GOS 4-5], and secondary endpoints were functional independence measure (FIM) score and mortality rate at 6 and 12 months follow-up after recruitment.

RESULTS: A total of 107 patients were randomized into four groups (placebo [n = 27], progesterone [n = 26], hypothermia alone [n = 27], and progesterone + hypothermia [n = 27]). The study groups were comparable in baseline parameters except for a higher incidence of decompressive craniectomy in the placebo group (P = 0.001). The analysis of GOS at 6 months revealed statistically significant better outcome in the hypothermia group (82%; P = 0.01) and a weaker evidence for progesterone group (74%; P = 0.07) as compared with the placebo group (44%). However, the outcome benefit was marginal at 1-year follow-up for the hypothermia group (82% vs. 58%, P = 0.17). The adjusted odds ratio of poor recovery at 6 months in the hypothermia group was 0.21 (confidence interval = 0.05-0.84, P = 0.03), as compared with the placebo group. Although mean FIM scores at 6 and 12 months respectively were marginally higher in the hypothermia and progesterone groups compared with the placebo group (P = 0.06 and 0.27), the proportion of functionally independent individuals were similar in all the groups (P = 0.79 and 0.51). The mortality rates were similar in all the groups at 6 and 12 months (P = 0.78 and 0.52 respectively).

CONCLUSIONS: A strong evidence for prophylactic hypothermia and a weak evidence for progesterone therapy was observed for a better primary outcome at 6 months as compared to the placebo. A similar trend was observed at a 1-year follow-up. Contrary to our hypothesis, prophylactic hypothermia therapy suppressed the beneficial effects of progesterone therapy in sTBI patients. The complex cascades of factors responsible for such interactions are still unknown and need to be further determined.

Errataetall:

CommentIn: Neurol India. 2018 Mar-Apr;66(2):584-585. - PMID 29547211

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:65

Enthalten in:

Neurology India - 65(2017), 6 vom: 02. Nov., Seite 1304-1311

Sprache:

Englisch

Beteiligte Personen:

Sinha, Sumit [VerfasserIn]
Raheja, Amol [VerfasserIn]
Samson, Neha [VerfasserIn]
Goyal, Keshav [VerfasserIn]
Bhoi, Sanjeev [VerfasserIn]
Selvi, Arul [VerfasserIn]
Sharma, Pushpa [VerfasserIn]
Sharma, Bhawani Shankar [VerfasserIn]

Links:

Volltext

Themen:

4G7DS2Q64Y
Journal Article
Neuroprotective Agents
Progesterone
Randomized Controlled Trial

Anmerkungen:

Date Completed 11.07.2019

Date Revised 08.04.2022

published: Print

CommentIn: Neurol India. 2018 Mar-Apr;66(2):584-585. - PMID 29547211

Citation Status MEDLINE

doi:

10.4103/0028-3886.217973

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM278003389