Sickle cell disease: vaso-occlusive crisis: purified poloxamer 188 helped crisis resolution

Clinical bottom line (level 1b)

  1. Patients with sickle cell disease and an acute vaso-occlusive crisis who received purified poloxamer 188 compared with placebo were more likely to achieve crisis resolution after a week (NNT = 6 at 7 days) .
  2. There was no clear difference in the duration of the crisis between the two groups.
Orringer et al: JAMA 2001; 286 : 2099-2106
Expires May 2004

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 40 acute hospitals, USA

255 patients (aged 8 to 65; mean 21, 59% female) with sickle cell disease and a vaso-occlusive crisis requiring parenteral analgesia

Excluded if
  • aged < 8, > 65
  • renal or hepatic dysfunction
  • not on reliable contraception, pregnant or breastfeeding
  • clinically significant bleeding
  • chronic bacterial osteomyelitis
  • inadequate venous access
  • history of major surgery within 2 weeks
  • currently in hospital or admitted to hospital with pain within 2 weeks
  • in hypertransfusion program or another study
  • recent stroke or seizure, or other complications of sickle cell disease

Control Group: (n = 128, analysed): placebo
Experimental Group: (n = 127, analysed): purified poloxamer 188 loading dose 100 mg/kg for 1 hour followed by maintenance dose of 30 mg/kg for 47 hours
Patients could receive parenteral analgesia (morphine, hydromorphine, meperidine) but not NSAIDs during the infusion. Hydroxyurea could be continued.
86% followed for 7 days
Outcome notes:
  • crisis resolved : pain relieved for at least 4 hours, off parenteral analgesia for 12 hours, patient able to walk without difficulty and believed crisis had resolved

The evidence

Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
crisis resolved 7 days 45
(35.2%)		 65
(51.2%)		 46%
(9% to 95%)		 16.0%
(4.03% to 28.0%)		 6
(4 to 25)

Outcome Control Group
(SD)		 Experimental Group
(SD)		 Mean Difference
(95% CI)
duration of crisis (hours) 141.43
(41.90) 		132.62
(41.38) 		8.8
(-1.5 to 19)

Comments

  1. Patients were stratified for genotype and use of hydroxyurea before randomisation.
  2. No difference in pain scores or analgesia use was noted between the two groups.

Citation

  1. Orringer EP, Casella , Ataga KI, et al: purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: a randomized controlled trial. JAMA 2001; 286 : 2099-2106
Search Terms: from ACP Journal Club other articles noted
Contributor: Chris Ball, May 2002
Reviewer:

Clinical Question.
Patient sickle cell disease and vaso-occlusive crisis
Intervention or Exposure purified polaxamer compared with placebo
Outcome duration of crisis, pain