Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04616846 |
| Other study ID # |
2020/20 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 4, 2020 |
| Est. completion date |
January 25, 2022 |
Study information
| Verified date |
March 2022 |
| Source |
Centre Antoine Lacassagne |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Study Rational
Since December 2019, outbreak of COVID-19 caused by a novel virus SARS-Cov-2 has spread
rapidly around the world and became a pandemic issue. First data report high mortality in
severe patients with 30% death rate at 28 days. Exact proportions of the reasons of death are
unclear: severe respiratory distress syndrome is mainly reported which can be related to
massive cell destruction by the virus, bacterial surinfection, cardiomyopathy or pulmonary
embolism. The exact proportion of all these causes is unknown and venous thromboembolism
could be a major cause because of the massive inflammation reported during COVID-19.
High levels of D-dimers and fibrin degradation products are associated with increased risk of
mortality and some authors suggest a possible occurrence of venous thromboembolism (VTE)
during COVID-19.
Indeed, COVID-19 infected patients are likely at increased risk of VTE. In a multicenter
retrospective cohort study from China, elevated D-dimers levels (>1g/L) were strongly
associated with in-hospital death, even after multivariable adjustment.
Also, interestingly,the prophylactic administration of anticoagulant treatment was associated
with decreased mortality in a cohort of 449 patients, with a positive effect in patients with
coagulopathy (sepsis-induced coagulopathy score ≥ 4) reducing the 28 days mortality rate
(32.8% versus 52.4%, p=0.01).
However the presence/prevalence of VTE disease is unknown in COVID-19 cancer patients with
either mild or severe disease. Cancer patients are at a higher risk of VTE than general
population (x6 times) and could be consequently at a further higher of VTE during COVID-19,
in comparison with non-cancer patients.
The exact rate of VTE and pulmonary embolism during COVID-19 was never evaluated, especially
in cancer patients, and is of importance in order to understand if this disease needs
appropriate prophylaxis against VTE.
The largest series of cancer patients so far included 28 COVID-19 infected cancer patients:
the rate of mortality was 28.6%. 78.6% of them needed oxygen therapy, 35.7% of them
mechanical ventilation. Pulmonary embolism was suspected in some patients but not
investigated due to the severity of the disease and renal insufficiency, reflecting the lack
of data in this situation.
The aim of the present study is to analyze the rate of symptomatic/occult VTE in a cohort of
patients with cancer.
Expected benefits Anticipated benefits of the research are the detection of VTE in order to
treat it for the included patient.
For all COVID-19 positive cancer patients it will enable to provide some guidelines and
determine which patient are at risk for VTE and which will need ultrasound to detect occult
VTE.
Foreseeable risks Foreseeable risks for patients are non-significant because the additional
procedures needed are ultrasound exam, and blood sample test.
Methodology
Retrospective and prospective (ambispective), multicentric study to evaluate the occurrence
of venous thromboembolism during COVID-19 infection.
Indeed, because the outbreak can end within the next 3-6 months, Investigators may not be
able to answer the question if Investigators only focus on patients investigated
prospectively. Investigators then decided to include patients from medical team who are
already systemically screening patients with COVID-19 disease for VTE.
Trial objectives
Main objective To evaluate the rate of venous thromboembolism at 23 days during COVID-19
infection in cancer patients.
Description:
Study Rational
Since December 2019, outbreak of COVID-19 caused by a novel virus SARS-Cov-2 has spread
rapidly around the world and became a pandemic issue. First data report high mortality in
severe patients with 30% death rate at 28 days. Exact proportions of the reasons of death are
unclear: severe respiratory distress syndrome is mainly reported which can be related to
massive cell destruction by the virus, bacterial surinfection, cardiomyopathy or pulmonary
embolism. The exact proportion of all these causes is unknown and venous thromboembolism
could be a major cause because of the massive inflammation reported during COVID-19.
High levels of D-dimers and fibrin degradation products are associated with increased risk of
mortality and some authors suggest a possible occurrence of venous thromboembolism (VTE)
during COVID-19.
Indeed, COVID-19 infected patients are likely at increased risk of VTE. In a multicenter
retrospective cohort study from China, elevated D-dimers levels (>1g/L) were strongly
associated with in-hospital death, even after multivariable adjustment.
Also, interestingly, the prophylactic administration of anticoagulant treatment was
associated with decreased mortality in a cohort of 449 patients, with a positive effect in
patients with coagulopathy (sepsis-induced coagulopathy score ≥ 4) reducing the 28 days
mortality rate (32.8% versus 52.4%, p=0.01).
However the presence/prevalence of VTE disease is unknown in COVID-19 cancer patients with
either mild or severe disease. Cancer patients are at a higher risk of VTE than general
population (x6 times) and could be consequently at a further higher of VTE during COVID-19,
in comparison with non-cancer patients.
The exact rate of VTE and pulmonary embolism during COVID-19 was never evaluated, especially
in cancer patients, and is of importance in order to understand if this disease needs
appropriate prophylaxis against VTE.
The largest series of cancer patients so far included 28 COVID-19 infected cancer patients:
the rate of mortality was 28.6%. 78.6% of them needed oxygen therapy, 35.7% of them
mechanical ventilation. Pulmonary embolism was suspected in some patients but not
investigated due to the severity of the disease and renal insufficiency, reflecting the lack
of data in this situation.
The aim of the present study is to analyze the rate of symptomatic/occult VTE in a cohort of
patients with cancer.
Expected benefits Anticipated benefits of the research are the detection of VTE in order to
treat it for the included patient.
For all COVID-19 positive cancer patients it will enable to provide some guidelines and
determine which patient are at risk for VTE and which will need ultrasound to detect occult
VTE.
Foreseeable risks Foreseeable risks for patients are non-significant because the additional
procedures needed are ultrasound exam, and blood sample test.
Methodology
Retrospective and prospective (ambispective), multicentric study to evaluate the occurrence
of venous thromboembolism during COVID-19 infection.
Indeed, because the outbreak can end within the next 3-6 months, Investigators may not be
able to answer the question if Investigators only focus on patients investigated
prospectively. Investigators then decided to include patients from medical team who are
already systemically screening patients with COVID-19 disease for VTE.
Trial objectives
Main objective To evaluate the rate of venous thromboembolism at 23 days during COVID-19
infection in cancer patients.
Secondary objectives
The secondary objectives are:
1. To determine the 23-days rate of hospitalization due to venous thromboembolism;
2. To determine the 23-days Overall Survival (OS);
3. To determine the 23-days Specific Survival (SS, death due to venous thromboembolism);
4. To evaluate the global safety of antineoplastic treatment;
5. To determine the predictive factors of venous thromboembolism;
6. To compare the rate of symptomatic venous thromboembolism between the COVID-19 negative
and COVID-19 positive patients.
Ancillary study Collection of blood sample in order to detect thrombophilia in case of venous
thromboembolism.
Description of specifics procedure
For the prospective cohort:
Day 1 = Day when COVID-19 test is performed.
- Blood sample (Day 1 for every patient tested for COVID19 infection) three 1.8ml citrate
tubes, three 3ml Heparin and two 4 ml EDTA tubes:
- Count of Hb, platelet, leukocytes, neutrophils, lymphocytes,
- LDH, CRP, Procalcitonin, D-dimers, ferritin, fibrin degradation product, sodium,
potassium, ASAT, ALAT, GGT, PAL, TP, TCA,
- Bilirubin, calcium, protein, albumin, fibrinogen, troponin, BNP.
- 2 Peripheral venous Ultrasound (if positivity for COVID19 and if positive D-dimers, at
day 1-10 after diagnosis and day 20-23):
- analysis of femoral, popliteal, tibial and peroneal venous,
- analysis of venous where there is material/central catheters,
- analysis of any venous where there is symptom of VTE.
- ECG (the day of peripheral venous ultrasound)
- Computed-tomography scan with iodin contrast injection: if suspicion of pulmonary
embolism
- Transthoracic ultrasound (the day of peripheral venous ultrasound): if pulmonary emboly
signs and no availability or possibility to do computed-tomography scan: clinical emboly
sign are dyspnea, hemoptysis, chest pain, tachycardia, palpitations, ECG signs.
- Ancillary study = thrombophilia analysis if occurrence of VTE, five 10ml citrate tubes
and two 10 ml EDTA tubes : anti-thrombin 3, protein S deficit, protein C deficit,
homocystein, circulating anticoagulant, Antibody against beta 2 gp1, Antibody against
cardiolopin, Activated protein C resistance, mutation of Factor V and II of Leiden. The
thrombophilia analysis, as part of the routine practice, will be also performed in the
retrospective cohort and if occurrence of VTE.
- For patient negative for COVID-19 infection, a second test will be performed between
Day20-Day23 to confirm the negativity of COVID-19 exposure.
Of note: dedicated ultrasound device will be used only for COVID-19 infected patients.
Statistical analysis plan
All statistical analyses will be performed at alpha risk=5% in bilateral hypothesis by the
statistician of the Center Antoine Lacassagne using R.3.6 and SAS 9.4 software for windows.
The cumulative rate of VTE is about 2-4% over a period of 70 days in patients treated for
cancer and at the start of chemotherapy.
Major well known risk factors for VTE are: certain type of cancer (stomach, pancreas, lung,
lymphoma, gynecologic, genitourinary without prostate), body mass index ≥ 35, platelets count
≥ 350 000/mm3, Hemoglobin level < 10 gr/dL (or use of red cell growth factors), leucocyte
cell count > 11 000/mm3. 27% of patients present with low risk Khorana score (score 0) that
is 0.8% occurrence of VTE, 60.2% with intermediate risk (Khorana score of 1-2) that is 1.8%
occurrence of VTE and 12.8% high risk (Khorana score ≥ 3) that is 7.1% risk of VTE. Of note
the rate of occult VTE in patients with high risk is about 9% in a cohort of 35 patients.
The aim of the study is to describe the proportion of VTE in patients with cancer presenting
a COVID-19 infection.
We estimate that forty patients are needed to have an appropriate overview of the incidence
in COVID-19 patients. In order to compare with a similar non-infected cohort Investigators
will also include patients with cancer tested negative for COVID-19 during the same period
(as soon as possible, a serology will be used thereafter to confirm it). All patients with
cancer tested negative for COVID-19 will be included. Investigators estimate that 80 patients
are needed to have an appropriate overview of the rate of VTE in the control cohort. This
negative cohort will be further tested with serology as soon as available, to check if they
were tested as false negative.
