TC-325 (Hemospray, Cook Medical, Winston-Salem, North Carolina, USA) is a propriety mineral blend powder developed for the purpose of endoscopic hemostasis. The powder was originally approved for use in stopping bleeding from external wounds in both civilian and military injuries. In 2011, our group reported its first endoscopic application in patients with actively bleeding peptic ulcers.
1
The powder was sprayed onto the bleeding vessel with the use of a pressurized carbon dioxide canister. In 19 of 20 patients, hemostasis was achieved. The only patient in whom hemospray treatment failed underwent angiography, which showed a pseudoaneurysm of his left gastric artery. The aneurysm was successfully embolized. The endoscopic use of the powder appeals to many endoscopists because of the simplicity of the technique.There has been a growing interest in the application of hemospray. There have many published series,
2
, 3
, 4
, 5
, 6
including 2 national registries7
,8
about the endoscopic use of hemospray. The GRAPHE registry included 202 patients (61 tumors) and found a 96.5% rate of immediate hemostasis. Recurrent bleeding at day 30 was 33.5%. The Spanish multicenter registry of 261 patients reported a rate of 93.5% in intraprocedural success and a failure rate of 25% over 30 days. In that cohort, tumor bleeding accounted for 18.1% of all cases, and TC-325 was used predominantly for rescue purposes in 191 patients (73.2%). These case series were heterogenous in their case mix and the indications for use.There has been one small randomized controlled trial, which enrolled 20 patients.
9
The trial compared TC-325 with combined endoscopic injection with either hemoclips or heater probe. The rates of initial hemostasis and further bleeding were similar (9 vs 10 and 3 vs 1, respectively). The prevailing literature suggests that TC-325 should not be used as a monotherapy because of the high rate of recurrent bleeding. It is, however, efficacious in the acute control of bleeding and as a rescue therapy. It is generally recommended that after initial control with TC-325, a more definitive treatment should follow.TC-325 has recently been applied to variceal bleeding. Ibraham et al
10
randomized patients with variceal bleeding to receiving endoscopic spraying with TC-325 within 2 hours and elective endoscopy the next day. Both groups received vasoactive drugs on admission. In the TC-325 group, 5 of 43 patients required rescue therapy, and 1 patient had recurrent bleeding. In the control group, 13 of 43 patients required rescue endoscopic hemostasis for significant clinical bleeding (P = .034). The authors also found the survival difference at 6 weeks in favor of TC-325 use (mortality rate 7% vs 30%, P = .006).In a pilot study by Chen et al
11
in the current issue of Gastrointestinal Endoscopy, patients with bleeding upper or lower GI malignancies were randomized to receive TC-325 or the standard-of-care hemostatic treatment during endoscopy. The primary outcome was immediate hemostasis. With an intention-to-treat analysis, hemostasis was achieved in 9 of 10 patients in the TC-325 group and 4 of 10 patients in the standard-of-care group, respectively. Of 6 patients in whom endoscopic hemostasis with conventional treatments failed, 5 received TC-325. In the TC-325 group, 1 patient experienced failure of endoscopic treatment and died of exsanguination from a colon tumor that eroded into the inferior mesenteric artery. The volume of blood transfusion (mean 2.5 units to either group), the use of angiographic embolization (1 in either group), radiation (4 vs 3), and surgery (1 vs 2) were similar between groups.The authors should be commended for their efforts in conducting the first randomized controlled trial of the use of TC-325 in the treatment of malignant GI bleeding. The condition is uncommon. In the National U.K. Audit on the management of acute upper GI bleeding, malignancy accounted for 3.7% of all cases.
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Understandably, this pilot study took 2 years to complete. TC-325 appears uniquely suited for the purpose because of its noncontact and nontraumatic application. Tumor tissue is often friable and bleeding is often diffuse. The spraying can cover a large surface. For the first time, we have comparative data attesting the efficacy of TC-325 in tumor bleeding. The same group had in fact published 2 case series in 201213
and 201514
with 5 and 16 patients, respectively, reporting good effectiveness of hemospray in malignant GI bleeding.Recently, Pittayanon et al
15
conducted a study to compare the efficacy of hemospray and conventional treatment in tumor bleeding. Ten patients who received hemospray treatment were compared with matched patients with similar tumor types from a historical cohort. The recurrent bleeding rate at day 14 (and therefore the need for rescue intervention) were lower with the use of hemospray (1 vs 3). These results are promising because malignant GI bleeding is notoriously difficult to treat. Conventional endoscopic options include the use of thermal (contact and noncontact methods) or mechanical therapy in conjunction with injection therapy. Not only do there exist many treatment modalities, we encounter bleeding from different tumor types and morphologies. The reported rates of hemostasis with each modality vary across series. Thosani et al16
reported a 100% initial hemostasis in 10 patients with the use of argon plasma thermocoagulation. In another series by Martins et al,17
of 25 patients with upper GI tumors treated by the same modality, initial hemostasis was achieved in 73% of patients. In both series, further bleeding occurred in 1 of 3 patients. In a retrospective series of 113 patients who had upper GI bleeding from gastric cancers treated mainly with multipolar electrocoagulation or argon plasma coagulation, Kim et al18
showed rates of 44.2% and 55.8% for early and delayed bleeding, respectively.The purpose of conducting a pilot study is to examine the feasibility of a larger-scale randomized controlled trial or a definitive trial. A pilot study can be used to evaluate the feasibility of recruitment; randomization, especially in allocation concealment; assessment of procedures; and outcomes. The current pilot study provides an estimate of the primary outcome, albeit imprecise. If we were to extrapolate and calculate the sample size required for a full randomized controlled trial, a minimum of 19 patients would be required to detect a 40% difference in the rate of initial hemostasis (90% to 50%) with a power of 80% and a 2-sided type 1 error of 5%. The target sample size appears achievable within a reasonable time frame.
Ideally, treatment assignment should be known only to the endoscopist during endoscopy. This presents a logistic difficulty in obtaining consent, especially if the tumor is newly diagnosed at the procedure. In this pilot study, crossover to the other treatment arm was permitted if initial hemostasis was not possible. Five of 6 patients in whom conventional treatment failed were treated successfully with TC-325.
A crossover design allows for within-subject assessment and is said to promote internal validity. Unfortunately, the same design is prone to bias. Endoscopists with the prospect of crossing over to hemospray treatment may be less rigorous in applying the standard of care. In the current study, 5 of 10 patients received injection-alone therapy. There is also a carryover effect. It is easier to define treatment endpoint to hemospray treatment. We generally observe the sprayed area for 3 to 5 minutes. In the absence of further bleeding, we can then declare treatment success. By contrast, it is not so easy to define treatment success—or failure, for that matter—with other endoscopic treatment modalities. It is not unusual to see oozing at the end of endoscopic treatment when standard treatment is used. One can understand that TC-325 can be very effective in dealing with residual bleeding.
As aforementioned, tumor morphology may influence our choice of therapy. TC-325 may not work as well in a malignant ulcer with a large eroded artery in comparison with surface oozing from a fungating tumor. Although it is ethically difficult or impossible, should sham therapy be considered in the control group? In this trial, the follow-up therapies after endoscopic treatment were uncontrolled. Four of 7 patients after TC-325, as compared with 3 of 8 patients in the standard of care group, received radiation therapy within 30 days. One of 4 in the TC-325 group and 1 of 8 in the standard-of-care group underwent angiography. These treatments would have affected the outcomes and made comparison between groups difficult. The findings from this pilot randomized controlled trial have left us with many questions to ponder, specifically on the design of a definitive trial.
All in all, the medical literature suggests that TC-325 has a superior hemostatic effect in acute bleeding. It appears to be useful in a variety of bleeding conditions. Although TC-325 is still to be confirmed with a larger trial, this pilot randomized trial has provided evidence to support the addition of TC-325 to our usual repertoire in managing GI tumor bleeding.
Disclosure
All authors disclosed no financial relationships relevant to this publication.
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- TC-325 hemostatic powder versus current standard of care in managing malignant GI bleeding: a pilot randomized clinical trialGastrointestinal EndoscopyVol. 91Issue 2
- PreviewTC-325 (Hemospray; Cook Medical, Winston-Salem, NC, USA), an endoscopic hemostatic powder, exhibits possible benefits in patients with malignant GI bleeding. Our aim is to assess feasibility and determine estimates of efficacy of TC-325 compared with standard of care (SOC) in terms of initial hemostasis and recurrent bleeding rates in comparable groups of patients with malignant GI bleeding.
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