Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04836052 |
| Other study ID # |
MRC-04-20-1120 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
December 24, 2020 |
| Est. completion date |
December 24, 2021 |
Study information
| Verified date |
March 2021 |
| Source |
Hamad Medical Corporation |
| Contact |
Sandro Rizoli, PhD |
| Phone |
+97444396157 |
| Email |
srizoli[@]hamad.qa |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
COVID-19 infection has been widely spread since December 2019 and causing many comorbidities
and fatalities. The most common clinical presentation of COVID-19 patients admitted to ICUs
is respiratory failure , hypoxia and acute lung injury.
While new therapies and vaccines are urgently being investigated, they may take an inordinate
time to get to right people. Omega-3-oil has been shown to have less proinflammatory
mediators that may have immunomodulating, anti-inflammatory and antiviral effect. Two main
fatty acids in omega-3-oil including eicosapentaenoic acid and docosahexaenoic acid have
shown benefit in patients with ARDS as well.
So, the investigators proposed a randomized controlled study to evaluate the effectiveness of
omega-3-oil supplementation 2 gm PO/NGT/OGT twice daily for 28 days or till discharge or till
death in COVID-19 critically ill patients admitted to ICU who require oxygen support.
Description:
The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) due to a novel
coronavirus (COVID-19) has emerged from Wuhan, China in late December 2019 and spread rapidly
worldwide. Until July 16, 2020, there has been more than 13 million confirmed cases worldwide
and ~580,000 deaths attributed to the disease. With the fast evolution of this worldwide
public-health emergency, the general public has demanded the urgent investigation of
potentially beneficial drugs that may improve the outcome of those affected by SARS-CoV-2
infection. While new therapies and vaccines are urgently being investigated, they may take an
inordinate time, or never be identified. In the world today, there is only one drug approved
by the FDA for COVID-19 (Remdesivir), while the investigation of several other re-purposed
drugs is potentially suggested for SARS-CoV-2 treatment. Many trials are taking place around
the world, including some utilizing potentially dangerous drugs with considerable side
effects and enormous costs. However, the clinical effectiveness and safety of all
pharmacologic therapies so far have not been fully proven.
The preliminary findings about this disease indicates that patients with cardiovascular risk
factors including diabetes, obesity and other pre-existing cardiovascular diseases have worse
outcomes. Additionally, severe respiratory infection and hypoxia associate with severe
COVID-19 might trigger many pathological pathways which leads to cardiovascular sequelae. In
a cohort of 416 hospitalized patients with COVID-19, myocardial injury defined by an elevated
high sensitivity troponin I level was associated with in-hospital mortality. Another study of
187 hospitalized patients with COVID-19 showed a similar association. Interestingly, the
highest mortality rates were observed among patients with pre-existing cardiovascular
disease. Importantly, none of the published experiences from anywhere in the world has
explored omega-3 oil and its known protective cardiovascular benefits.
Omega-3 fatty acids are found in food such as fish and flaxseed as well as in dietary
supplements labeled omega-3-oil.The beneficiary role of Omega-3 polyunsaturated fatty acids
(PUFA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish, other
marine sources, and supplements, have been shown to be anti-inflammatory through several
cellular mechanisms including their incorporation into cellular membranes and resulting
altered synthesis of eicosanoids. There is the potential that arachidonic acid (AA,)
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and other dietary unsaturated
fatty acids can inactivate enveloped viruses. It is thought that these fatty acids and others
cause leakages or lysis of the viral envelopes by disrupting the membrane integrity, amongst
other potential mechanisms. Indeed, the supplementation of EPA and DHA raises the level of
these fatty acids in the phospholipids of cells involved in inflammation in a time and
dose-dependent fashion at the expense of AA4. Li and colleagues reviewed 89 systematic
reviews and meta-analyses investigating fish intake and all-cause mortality, concluding that
fish intake at 2-4 servings per week is associated with the largest risk reduction.
In animal models despite these potential positive effects, there is conflicting evidence in
relation to fish or fish oil consumption for some viral infections. In influenza models, fish
oil-fed mice demonstrated impaired resistance to influenza infection due to their
immunomodulatory and anti-inflammatory properties, which negatively dampened the immune
response of the mice against the infection. In another mouse model, fish oil intake delayed
influenza virus clearance and impaired the immune response in the lungs of mice by disrupting
interferon-γ and immunoglobulin A. A further study indicated that it may be due to the
impairment of virus-specific T lymphocyte cytotoxicity.
Despite the potential benefit, there are few human studies with omega 3 and immune and
inflammatory response. The recent proposed benefit for omeg-3-oil is unique, EPA and DHA
which are main fatty acids in omega-3-oils may act as substrates for the synthesis of
specialized pro-resolving lipid mediators such as maresins, resolvins, and protectins, of
which protectins may reduce the replication of influenza and potentially affect the
inflammatory manifestations of respiratory viral diseases.
Notably, an in vitro model of human cells (Huh-7 and VeroE6) infected with a human
coronavirus (HCoV-229E) demonstrated that several bioactive lipids downstream of
phospholipase A2 (PLA2) activation were upregulated by the host cells. It is postulated that
coronaviruses modulate the host lipid profile to optimize and maintain a specific homeostasis
for viral replication. However, exogenous supplementation of AA and linoleic acid suppressed
viral replication by interfering with the optimal host lipid conditions for viral
replication. Notably, exogenous supplementation of AA and linoleic acid was also conserved
when human cells were infected with MERS. However, exogenous supplementation of AA and
linoleic acid suppressed viral replication by interfering with the optimal host lipid
conditions for viral replication. Notably, exogenous supplementation of AA and linoleic acid
was also conserved when human cells were infected with MERS. EPA, DHA, and AA also inhibited
the replication of enterovirus A71 and coxsackievirus A16.While it is suggested that the oral
or intravenous administration of various bioactive lipids could potentially reduce the
severity and/or enhance the recovery of those infected with COVID-19, a dietary prophylactic
approach or a dietary strategy for recovering patients is also worth considering. Further
research is certainly required, as increasing AA via the diet might seem counterintuitive, as
it is mainly proinflammatory.
Other clinical research about several lung infections, found the administration of PUFA can
improve the outcome of the patient in acute pneumonia. Recent study reported that the dietary
supplementation of ω-3 PUFA can exert an overall beneficial effect against acute pneumonia
through the upregulation of the host's specific and nonspecific immune defenses.
Inflammation resolution is strongly dependent on lipid mediators, the specialized
pro-resolution mediators (SPMs). As mentioned above, omega-3 polyunsaturated fatty acids (n-3
PUFAs) are precursors of very potent SPMs, including resolvins, protectins and maresins. In
addition, they are associated with a less aggressive inflammatory initiation, after competing
with omega-6 fatty acids for eicosanoid synthesis. Therefore, it makes sense to consider the
use of n-3 PUFAs for clinical management of COVID-19 patients.
Recent clinical studies In ARDS patients, the enteral use of n-3 PUFAs has been associated to
oxygenation improvement, reduced duration of mechanic ventilation as well as shorter ICU
length of stay. In another study, critically ill patients receiving parenteral nutrition
therapy enriched with fish oil lipid emulsion (rich in n-3 PUFAs EPA and DHA) were reported
to have decreased infection and sepsis risk (40% to 56%, respectively) and a reduction of
length of hospital and ICU stay by about two day.
As eluded previously, 2 cohort studies from China indicate that a significant proportion of
hospitalized patients with COVID-19 developed some degree of myocardial injury. Coronary
atherosclerotic plaques are more prone to rupture in response to an exacerbated inflammatory
response during SARS-CoV-2. The use of n-3 FA (4-6 g/d) for improving atherosclerotic
cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25%
reduction in major adverse cardiovascular events in REDUCE-IT.
Furthermore, several drugs will increase triglyceride concentrations in patients with
underlying high triglycerides. The effects of n-3 FA on drug-induced HTG have received
relatively little attention, but n-3 FAs have uniformly been reported to lower triglycerides
when used with interferon-α, antipsychotics, l-asparaginase, oral estrogens, protease
inhibitors, retinoic acid, and sirolimus. In contrast with COVID-19 there is scarce of
information published till now about role of n-3 FAs.
Collectively, these findings suggest that omega-3 fatty acids have properties that could
improve oxygenation and outcome of COVID-19 patients. The utilization of omega-3-oil as safe,
available and inexpensive therapy could be a promising therapeutic approach against
SARS-CoV-2. Moreover, recent analysis of 8 studies showed that consumption of omega 3 oil up
to 10 gm per day is safe in ICU.
However, due to lack of sufficient clinical data supporting either the beneficial or harmful
effects of omega-3 oil use in patients with COVID-19, the optimal strategy for the management
of in COVID-19 is uncertain and remains to be elucidated - putting together all the known
properties of omega 3 and what is known about the COVID-19, the investigators hypothesize
that omega 3 could have a significant beneficial impact on the clinical outcome of infected
patients. The aim of this study is to investigate in-hospital use of omega-3 oil and
mechanical ventilator days, improvement in oxygenation, need for ventilator in non-ventilated
patients, ICU- length of stay, hospital related length of stay, thrombosis, all-cause
morbidity and mortality in COVID-19 patients in a in randomized prospective controlled trial.
There is no study or evidence on Omega 3 and COVID-19 infection and respiratory failure. The
investigators propose a randomized controlled study to minimize the risk of bias and
confounding factors.
