Study protocol for a randomized, blinded, controlled trial of ketamine for acute painful crisis of sickle cell disease

Abstract

Background Sickle cell disease (SCD) is an inherited hematological disorder where the shape of red blood cells is altered, resulting in the destruction of red blood cells, anemia, and other complications. SCD is prevalent in the southern and eastern provinces of the Arabian peninsula. The most common complications for individuals with SCD are acute painful episodes that require several doses of intravenous opioids, making pain control for these individuals challenging. Instead of opioids, some studies have suggested that ketamine might be used for pain control in acute pain episodes of individuals with SCD. This study aims to evaluate whether the addition of ketamine to morphine can achieve better pain control, decreasing the number of repeated doses of opiates. We hypothesize that early administration of ketamine would lead to a more rapid improvement in pain score and lower opioid requirements. Methods and analysis This study will be a prospective, randomized, concealed, blinded, pragmatic parallel group, controlled trial enrolling adult patients with SCD and acute vaso-occlusive crisis pain. All patients will receive standard analgesic therapy during evaluation. Patients randomized to the treatment arm will receive low-dose ketamine (0.3 mg/kg in 0.9% sodium chloride, 100 ml bag) in addition to standard intravenous hydration, while those in the control group will receive a standard dose of morphine (0.1 mg/kg in 0.9% sodium chloride, 100 ml bag) in addition to the standard intravenous hydration. All healthcare providers will be blinded to the treatment arm. Data will be analyzed according to the intention-to-treat principle. The primary outcome is improvement in pain severity using the Numerical Pain Rating Score. Trial registration Clinicaltrials.gov, NCT03431285 . Registered on 13 February 2018 Electronic supplementary material The online version of this article (10.1186/s13063-019-3394-4) contains supplementary material, which is available to authorized users.

Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial

“…Ketamine opioid-sparing effect has been demonstrated in some trials and retrospective studies mainly for ICU patients admitted for postoperative reasons and trauma [ 20 , 22 , 34 ]. In contrast, other trials did not show opioid-sparing effect [ 30 , 35 , 36 ] (Additional file 1 : Table S9). In our pilot, there was no difference in amount of sedatives or opioids and underlying reasons are likely multifactorial.…”

Ketamine administration for acute painful sickle cell crisis: A randomized controlled trial

“…We registered the trial protocol online (Clinicaltrials.gov registration NCT03431285) and, subsequently, published the full protocol. 34 All authors affirm the accuracy and completeness of the data and adherence to the approved protocol.…”

Management of refractory chronic pain in sickle cell disease with intrathecal drug delivery system

“…The fight against pain in SCD is studied on several approaches, including drugs already in use in the clinical routine such as Hydroxyurea, Pregabalin, Ketamine, as well as biological ones with blood transfusion and the development of new drugs such as crizanlizumab and of L-Glutamine. 14 , 15 , 16 , 17 , 18 , 19 , 20 In a double-blind, placebo-controlled study, crizanlizumab (humanized anti-P-selectin monoclonal antibody) showed promise as a medication to prevent VOC, although it did not show a reduction in the rate of hospitalization days. 18 , 19 In November 2019, this drug received FDA approval in the USA, being indicated to reduce the frequency of VOC in individuals aged ≥ 16 years and diagnosed with SCD.…”