Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial.

BACKGROUND: The risk of death from spontaneous intracerebral haemorrhage is increased for people taking antiplatelet drugs. We aimed to assess the feasibility of randomising patients on antiplatelet drug therapy with spontaneous intracerebral haemorrhage to desmopressin or placebo to reduce the antiplatelet drug effect. METHODS: DASH was a phase 2, randomised, placebo-controlled, multicentre feasibility trial. Patients were recruited from ten acute stroke centres in the UK and were eligible if they had an intracerebral haemorrhage with stroke symptom onset within 24 h of randomisation, were aged 18 years or older, and were taking an antiplatelet drug. Participants were randomly assigned (1:1) to a single dose of intravenous desmopressin 20 µg or matching placebo. Treatment allocation was concealed from all staff and patients involved in the trial. The primary outcome was feasibility, which was measured as the number of eligible patients randomised and the proportion of eligible patients approached, and analysis was by intention to treat. The trial was prospectively registered with ISRCTN (reference ISRCTN67038373), and it is closed to recruitment. FINDINGS: Between April 1, 2019, and March 31, 2022, 1380 potential participants were screened for eligibility. 176 (13%) participants were potentially eligible, of whom 57 (32%) were approached, and 54 (31%) consented and were subsequently recruited and randomly assigned to receive desmopressin (n=27) or placebo (n=27). The main reason for eligible patients not being recruited was the patient arriving out of hours (74 [61%] of 122 participants). The recruitment rate increased after the enrolment period was extended from 12 h to 24 h, but it was then impaired due to the COVID-19 pandemic. Of the 54 participants included in the analysis (mean age 76·4 years [SD 11·3]), most were male (36 [67%]) and White (50 [93%]). 53 (98%) of 54 participants received all of their allocated treatment (one participant assigned desmopressin only received part of the infusion). No participants were lost to follow-up or withdrew from the trial. Death or dependency on others for daily activities at day 90 (modified Rankin Scale score >4) occurred in six (22%) of 27 participants in the desmopressin group and ten (37%) of 27 participants in the placebo group. Serious adverse events occurred in 12 (44%) participants in the desmopressin group and 13 (48%) participants in the placebo group. The most common adverse events were expansion of the haemorrhagic stroke (four [15%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group) and pneumonia (one [4%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group). INTERPRETATION: Our results show it is feasible to randomise patients with spontaneous intracerebral haemorrhage who are taking antiplatelet drugs to desmopressin or placebo. Our findings support the need for a definitive trial to determine if desmopressin improves outcomes in patients with intracerebral haemorrhage on antiplatelet drug therapy. FUNDING: National Institute for Health Research.

Major trauma from suspected child abuse: a profile of the patient pathway.

BACKGROUND: Networked organised systems of care for patients with major trauma now exist in many countries, designed around the needs of the majority of patients (90% adults). Non-accidental injury is a significant cause of paediatric major trauma and has a different injury and age profile from accidental injury (AI). This paper compares the prehospital and inhospital phases of the patient pathway for children with suspected abuse, with those accidentally injured. METHODS: The paediatric database of the national trauma registry of England and Wales, Trauma Audit and Research Network, was interrogated from April 2012 (the launch of the major trauma networks) to June 2015, comparing the patient pathway for cases of suspected child abuse (SCA) with AI. RESULTS: In the study population of 7825 children, 7344 (94%) were classified as AI and 481 (6%) as SCA. SCA cases were younger (median 0.4 years vs 7 years for AI), had a higher Injury Severity Score (median 16vs9 for AI), and had nearly three times higher mortality (5.7%vs2.2% for AI). Other differences included presentation to hospital evenly throughout the day and year, arrival by non-ambulance means to hospital (74%) and delayed presentation to hospital from the time of injury (median 8 hours vs 1.8 hours for AI). Despite more severe injuries, these infants were less likely to receive key interventions in a timely manner. Only 20% arrived to a designated paediatric-capable major trauma centre. Secondary transfer to specialist care, if needed, took a median of 21.6 hours from injury(vs 13.8 hours for AI). CONCLUSION: These data show that children with major trauma that is inflicted rather than accidental follow a different pathway through the trauma system. The current model of major trauma care is not a good fit for the way in which child victims of suspected abuse present to healthcare. To achieve better care, awareness of this patient profile needs to increase, and trauma networks should adjust their conventional responses.

Antifibrinolytic drugs for acute traumatic injury.

BACKGROUND: Uncontrolled bleeding is an important cause of death in trauma victims. Antifibrinolytic treatment has been shown to reduce blood loss following surgery and may also be effective in reducing blood loss following trauma. OBJECTIVES: To assess the effect of antifibrinolytic drugs in patients with acute traumatic injury. SEARCH METHODS: We ran the most recent search in January 2015. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), PubMed and clinical trials registries. SELECTION CRITERIA: Randomised controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA], epsilon-aminocaproic acid and aminomethylbenzoic acid) following acute traumatic injury. DATA COLLECTION AND ANALYSIS: From the results of the screened electronic searches, bibliographic searches, and contacts with experts, two authors independently selected trials meeting the inclusion criteria, and extracted data. One review author assessed the risk of bias for key domains.Outcome measures included: mortality at end of follow-up (all-cause); adverse events (specifically vascular occlusive events [myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism] and renal failure); number of patients undergoing surgical intervention or receiving blood transfusion; volume of blood transfused; volume of intracranial bleeding; brain ischaemic lesions; death or disability.We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach. MAIN RESULTS: Three trials met the inclusion criteria.Two trials (n = 20,451) assessed the effect of TXA. The larger of these (CRASH-2, n = 20,211) was conducted in 40 countries and included patients with a variety of types of trauma; the other (n = 240) restricted itself to those with traumatic brain injury (TBI) only.One trial (n = 77) assessed aprotinin in participants with major bony trauma and shock.The pooled data show that antifibrinolytic drugs reduce the risk of death from any cause by 10% (RR 0.90, 95% CI 0.85 to 0.96; P = 0.002) (quality of evidence: high). This estimate is based primarily on data from the CRASH-2 trial of TXA, which contributed 99% of the data.There is no evidence that antifibrinolytics have an effect on the risk of vascular occlusive events (quality of evidence: moderate), need for surgical intervention or receipt of blood transfusion (quality of evidence: high). There is no evidence for a difference in the effect by type of antifibrinolytic (TXA versus aprotinin) however, as the pooled analyses were based predominantly on trial data concerning the effects of TXA, the results can only be confidently applied to the effects of TXA. The effects of aprotinin in this patient group remain uncertain.There is some evidence from pooling data from one study (n = 240) and a subset of data from CRASH-2 (n = 270) in patients with TBI which suggest that TXA may reduce mortality although the estimates are imprecise, the quality of evidence is low, and uncertainty remains. Stronger evidence exists for the possibility of TXA reducing intracranial bleeding in this population. AUTHORS' CONCLUSIONS: TXA safely reduces mortality in trauma patients with bleeding without increasing the risk of adverse events.  TXA should be given as early as possible and within three hours of injury, as further analysis of the CRASH-2 trial showed that treatment later than this is unlikely to be effective and may be harmful. Although there is some promising evidence for the effect of TXA in patients with TBI, substantial uncertainty remains.Two ongoing trials being conducted in patients with isolated TBI should resolve these remaining uncertainties.