TAPS
The TAPS study is now complete.
Chief investigators: Lorna Williamson and Professor Dame Sally Davies
Primary sponsor: NHSBT
Funder: The trial is funded by a Project Grant from NHSBT, awarded by the National Research and Development Committee.
Summary
Sickle cell disease (SCD) patients often require surgery, particularly abdominal, orthopaedic or ENT procedures because of conditions such as obstructive sleep apnoea, adenotonsillar hypertrophy, cholelithiasis, splenic sequestration and avascular necrosis. Whilst the rate of peri-operative complications is variable, depending on clinical severity and type of operation, both sickle related and non-sickle related complications are common.
Pre-operative blood transfusion, which decreases the percentage of sickle red cells, suppresses erythropoiesis and improves anaemia, has been associated with decreased sickle complications but is also associated with acute transfusion reactions, allo-immunisation, and delayed haemolytic transfusion reactions.
There is increasing recognition that transfusion may be immuno-suppressive, increasing the risk of post-operative infections. Although the risk of post-transfusion HIV or hepatitis is low in the developed world, they remain high in Sub-Saharan Africa, and with potential new transfusion hazards such as variant Creutzfeld-Jacob disease and West Nile virus, the risks of transfusion need to be balanced against its apparent benefits.
Whilst several observational studies showed a benefit of transfusion, others showed no benefit and studies from countries where blood is less available, or from centres which tend not to offer pre-operative blood transfusion did not show higher peri-operative complication rates.
Improved surgical and anaesthetic techniques have decreased peri-operative complications and a UK survey of surgery in sickle patients in 2002-3 showed large variation in transfusion practice, with 43% of patients receiving no pre-operative transfusion. Similar variation in practice occurs in US.
Given the equipoise existing regarding the necessity of pre-operative blood transfusion4 a multi-centre trial was set up to assess whether routine pre-operative transfusion increases or decreases the overall peri-operative complication rate.
Study hypothesis
No consensus exists on the benefits of pre-operative transfusion in patients with Sickle Cell Disease (SCD). The aim of this trial was to establish the effect of pre-operative transfusion on peri-operative complication rates.
Study design
TAPS was designed as a multi-centre randomised group sequential superiority trial in which HbSS or HbSβ0thal patients aged one year or more and scheduled for low or medium risk surgery were randomised to receive no pre-operative transfusion (Arm A) or pre-operative transfusion (Arm B).
The primary outcome was the proportion of patients with clinically significant complications between randomisation and 30 days post-surgery.
Findings
The trial closed early due to an excess of patients experiencing Serious Adverse Events (SAEs) in Arm A – non-transfused (10 vs 1 in Arm B - transfused) with all but one patient having Acute Chest Syndrome (ACS).The majority of patients were HbSS 97% (65/67) having medium risk surgery 80.6% (54/67). The primary Intention To Treat analysis included 67 patients, and analysis of the primary outcome via logistic regression yielded an unadjusted odds ratio (OR) of 3.8 (95% CI: 1.2-12.2. P=0.027).
In Arm A 39.4% (13/33) of patients had significant complications compared to 14.7% (5/34) in Arm B (P=0.023). The proportion of patients who received intra-operative or post-operative transfusion was higher in Arm A compared to Arm B (36.4% (12/33) vs 8.8% (3/34)). Only one patient (Arm B) had developed red cell allo-antibodies by 3 months post-operatively. No differences in length of stay or re-admission rates were seen between arms.
Sickle cell patients (HbSS or HbSβ0thal) were recruited to the TAPS trial if they were going to have low or medium risk planned surgery. The aim of this trial was to find out whether blood transfusion should be given to patients with Sickle Cell Disease (SCD) before routine surgery or not.
The trial recruited from 22 sites in the UK, the Netherlands, Canada and Ireland. A decision to close the trial early was taken in March 2011 following a review of patient safety data as there were more serious complications during and after surgery in patients who did not receive a pre-operative transfusion than in those that did.
Although the trial closed early with 70 patients recruited rather than the 400 expected, the results were so clear that this information can be used as clinical evidence to help doctors make decisions about whether or not sickle patients should be given a transfusion before surgery.
The trial showed patients who did not receive a transfusion before surgery were more likely to have complications after their operation.
The TAPS trial team recommend that patients having medium risk planned surgery should be offered a transfusion before the planned surgery, and that these results should be taken into consideration when deciding whether or not patients having low risk surgery or with other genotypes should have a transfusion before their operation.
Publications
Howard J, Malfroy M, Llewelyn C, Choo Louise, Hodge, R, Johnson T, Purohit, S, Rees DC, Tillyer, L, Walker, I, Fijnvandraat, Kirby-Allan, M, Davies S, Williamson L. Transfusion Alternatives Preoperatively in sickle cell disease (TAPS): a randomised controlled multi-centre trial. Lancet 2013; 381:930-938. [Epub 23 Jan 2013 doi:10.1016/S0140-6736(12)61726-7]
Spackman E, Sculpher M, Howard J, Malfroy M, Llewelyn C, Choo L, Hodge R, Johnson T, Rees C, Fijnvandraat, K, Kirby-Allen M, Davies S and Williamson L. Cost-effectiveness analysis of preoperative transfusion in patients with sickle cell disease using evidence from the TAPS trial. Eur J Haematology [Epub 03 Nov 2013 doi:10.1111/ejh.12232]