December 9, 2022

Dr RR Baliga’s ‘Got Knowledge Doc’ PodKasts for Physicians| CARAVAGGIO Trial: Is Apixaban safe and efficacious in cancer Venous Thromboembolism?-NEJM April 2020 | Not Medical Advice or Opinion

Tabali guy here this podcast is on the new england journal of medicine april 23rd 2020 article titled apixaban for the treatment of venous thromboembolism associated cancer and is authored by dr. ag nelly and the qiraji o investigators on a sidebar who is ker-rah geo garagiola was a 16th to 17th century italian painter and in fact caravaggio is the name of

The artists hometown in lombardy in northern italy what was he famous for he was a leading italian painter of the late 16th and early 17th centuries who became famous for the intense and unsettling realism of his large-scale religious works recent guidelines have recommended the use of oral doxa ban our rivaroxaban for treatment of venous thromboembolism in

Patients with cancer however the benefit of these two oral agents is limited by the increased risk of bleeding associated with their use keeping this in mind the caravaggio investigators conducted a multinational randomized parallel invested initiated open label non-inferiority trial with blinded central outcome adjudication cancer patients with proximal deep

Vein thrombosis or pulmonary embolus were randomized to apixaban there were 576 in the apixaban group was the delta perrin and there were 579 patients in the delta parent group the ap in the epic sabayon our subjects received 10 milligram twice daily for seven days and then 5 milligram twice daily from seven days until six months in the diaper on all subjects

Received 200 internally units per kilo subcutaneous daily for seven days then 150 international units per kilo sub cadenas daily from seven days until six months the total number of enrollees was 1170 the duration of allah was six months mean patient age was 67 years and the percentage of females was 49 percent what was the inclusion criteria symptomatic or

Incidental proximal lower limb deep vein thrombosis symptomatic primary embolus are incident upon mary embolus in a segmental or more proximal femoral artery active cancer or history of cancer within last two years maximum proportion of patients in meeting the c inclusion criteria criterion was set at 20% what was the exclusion criteria age less than 18 years

Eastern cooperative oncology group performance status 3 or 4 life expectancy less than 6 months therapeutic doses of low molecular weight heparin fondren or unfractionated heparin or vitamin k antagonist over on for 72 hours before randomization indication for anticoagulant treatment other than index venous thromboembolism concomitant use of strong inhibitors

Or induces of sip 3a for or p-glycoprotein or concomitant p2y 12 inhibitor therapy such as clopidogrel procedural attack agrella or aspen therapy active bleeding or high-risk bailey anemia and thrombocytopenia for other exclusion criteria what were the principal findings of the study the primary outcome that is recurrent proximal deep vein thrombosis pulmonary

Embolism occurred in 5.6 percent of the patients in the epoxy bond group compared with 7.9 percent of the delta pattern group p-value for superiority equals 0.08 for non inferior less than 0.001 the primary safety outcome that is bleeding by european medicine agency ema definition occurred in 3.8 percent of the apex ban group compared with 4.0 of the delta

Parent group p-value equals zero point six zero secondary outcomes recurrent dvt – 0.3 percentage of the apixaban group compared with 2.6 percent of the delta parent group recurrent pe 3.3 percent of the apex of an group compared with 5.5 of the delta parent group fatal pulmonary embolism 0.7 percent of the attacks occur band group compared with 0.5 percent

Of the delta parent group and major gi bleeding 1.9 percent of the apixaban group compared with 1.7 percent of the delta parent group what did the investigators conclude among cancer patients with proximal dvt or pe the pixi ban was non-inferior compared to subcutaneous delta parent on prevention of recurrent venous thromboembolism there was no increase in

Major bleeding or gi bleeding among cancer patients treatment guidelines recommend now low molecular weight heparin doxa ban or river rocks are bad however he talks a ban and river ox a ban have been associated with increased incidence of gi bleeding they go on to say for some cancer patients with proximal dvt or pe impacts band twice-daily therapy would be

An appropriate therapeutic option in an accompanying editorial in the new england journal of medicine dr. agnes lee md from british columbia make some really important comments and observations on this on this paper she says these results compared favorably with those of prior trials of he talks of an and of rocks a ban in terms of bleeding relative to low

Molecular weight heparin she notes that this trial excluded patients with primary and metastatic brain lesions and include few patients with cancers of upper gi t and hematologic cancers the atom vt trial in which epic seban was evaluated the invite investigators found no major bleeding events with the pixi band but it was a smaller study with an enrollment

Of 300 patients it included patients with other thrombotic sites example of upper extremity and the overall mortality 13.2% was much lower than another trials which suggests patient selection she goes on to say the evidence of these trials makes a compelling case for adding a pixel ban as another anticoagulant option for the therapy of venous thromboembolism in

Cancer patients however she cautions given the heterogeneity of available trials it’s inappropriate to conclude that one direct oral anticoagulant that this doe ak is better than another without head-to-head comparison she so she asked the question how do we choose which anticoagulant to use and she responds carefully she recommends that the practicing clinician

Relies on detailed medical and clinical history ascertain the cancer type the status and treatment along with bleeding risk concomitant medications and shared decision-making with the patient patient experiences and values are important for example patients with primary brain tumors she goes on to say the known intracerebral metastasis or acute leukemia were

Excluded from participating in the qiraji trial but not from the hokusai vt cancer trial or the selectee trial he doxepin was evaluating the hokusai pt cancer trial and rivaroxaban was evaluated the select d trial for patients party to the adductor ban an initial week of low molecular weight heparin is required although fewer drug drug interactions are expected

Then with epic seban or rock or rivaroxaban she comments that very few new newer cancer therapies such as checkpoint inhibitors were included in all these trials and depending on the specific doe ak studied in each trial patients were receiving strong induces or inhibitors of p glycoprotein or sip 3a for per often excluded low molecular weight heparin is preferred

She says in patients in whom drug-drug interaction is a concern and in those who have undergone surgery involving the upper gi tract the cause absorption of all doe acts occur in the stomach and proximal sub small bowel in our experience with low molecular weight heparin in patients with bleeding or thrombocytopenia recurrent venous thromboembolism cns cancers

Or severe renal impairment and those with the perioperative setting will keep this parent early agent in use and she goes on to say warfarin still other role particularly in patients of major financial health care burdens finally given the terrain of cancer therapy is rapidly evolving the choice of antique oil in therapy will need to keep pace it’s important to

Keep in mind that this trial was limited to an initial six-month treatment of venous thromboembolism and patients with cancer more studies are required to determine whether there’s additional clinical benefit or for more extended duration of therapy for women strom barbarism in these patients in patients younger than 65 years of age he picks the van were shown

To be more effective than delta peron and preventing recurrent venous thromboembolism this apparent decrease in efficacy with increasing age that was shown in the subgroup analysis the authors say should be considered as hypothesis-generating and merits further study another additional point was this was an open labor trial to avoid the use of parental percy

Before six months but the authors argue that the number of suspected recurrences of venous thromboembolism was similar in both the treatment groups and all suspected trial outcome events were centrally adjudicated in a blinded manner and thirdly as in large majority of studies the authors say regarding the therapy of venous thromboembolism the sample size of

This trial was powered for the primary heart cup which is recurrent venous thromboembolism and was not powered to make definite of conclusions about bleeding the final takeaway is ola picks a band is non inferior to subcutaneous delta parent for treatment of cancer so cell venous thromboembolism without an increased risk of major bleeding

Transcribed from video
CARAVAGGIO Trial: Is Apixaban safe and efficacious in cancer Venous Thromboembolism?–NEJM April… By The Support Team MasterMedFacts