Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03428711 |
| Other study ID # |
METRO |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 26, 2018 |
| Est. completion date |
September 21, 2024 |
Study information
| Verified date |
February 2023 |
| Source |
Quovadis Associazione |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The objective of the study is to demonstrate the superiority of the mesoglycan (Prisma®),
compared to placebo, in reducing the incidence of thromboembolic complications (relapse /
extension of superficial venous thrombosis (SVT), deep venous thrombosis (DVT), pulmonary
embolism (PE)) in patients who have completed the cycle of therapy of the acute phase after
superficial vein thrombosis.
Description:
Rationale: SVT is a relatively common clinical condition, with recent evidence of association
with the development of DVT and / or pulmonary embolism that has changed the perception of
the risk of this disease (with conflicting data in the literature: 3-33 %). Previous natural
history studies have observed that thromboembolic complications (relapse / extension of SVT,
DVT, PE) can affect up to 10-15% of subjects at 3-6 months from the initial event, despite
adequate treatment of the acute phase. There are no literature studies that have
prospectively investigated the usefulness of drug therapy in secondary prevention of SVT once
the initial therapeutic cycle is completed.
Objective: To demonstrate the superiority of the mesoglycan (Prisma®), compared to placebo,
in reducing the incidence of thromboembolic complications (relapse / extension of superficial
venous thrombosis (SVT), deep venous thrombosis (DVT), pulmonary embolism (PE)) in patients
who have completed the cycle of therapy of the acute phase after superficial vein thrombosis.
Investigators: 18 Italian centers with proven experience in the treatment and prevention of
venous thromboembolic disease.
Study Design:
Phase II, multicentre, randomized, double-blind superiority study comparing mesoglycan
(Prisma®) 50 mg and placebo, both in double oral daily intake.
Study treatment:
Experimental drug: mesoglycan (Prisma®), already used in the treatment of chronic venous
ulcers, is a complex mucopolysaccharide, composed of a mixture of glycosaminoglycans (mainly
heparan-sulphate, dermatan sulfate), inhibitors of thrombin and of Factor Xa and active in
restore flow-mediated vasodilation.
Used in oral formulation, hard capsules, 50 mg, twice-a-day, for 12 months. Reference
therapy: placebo, organoleptically indistinguishable from the experimental drug, twice-a-day,
for 12 months.
Masking: the study is conducted in "double-blind".
Methodology and phases of the study:
Written Consent Collection: the investigator will inform the interested party that
participation in the study is voluntary and that the refusal will not lead to the loss of any
benefit or in any way affect the relationship with the doctor. Furthermore, it will be
announced that withdrawal from the study is possible at any time without having to provide a
specific reason. Before being enrolled in the study, each subject will receive a complete
explanation of the nature and purpose of the study by the investigator, along with a
description of the benefits and risks associated with participation. Insurance coverage will
also be mentioned and related procedures in case of injuries will be explained. A clear
information sheet will be delivered to the subject covering all the important aspects of the
study. Once read, the subject will have the opportunity to ask questions and sufficient time
will be given to consider the various aspects presented, before being asked to sign and date
the informed consent form.
The original copy of the signed and dated informed consent form will be kept by the
investigator in the "study file" kept in the Center. The subject will receive a copy of the
informed consent form signed and dated for future reference.
Screening: after obtaining written informed consent, all potential subjects will complete the
screening visit. If they satisfy the prefixed inclusion and exclusion criteria, they will be
enrolled in the study and will be subjected to ultrasound study using by color-coded duplex
ultrasonography (CCDU) of the lower limbs (investigation in standard clinical practice
because at the end of the treatment of the acute phase), to exclude a concomitant involvement
of the deep venous circle, or an extension of the initial SVT, which would imply the
extension of parenteral anticoagulant therapy. A blood test will be performed to determine
complete blood count, ALT, AST, creatinine, PT-INR, aPTT and PCR.
Randomization: centralized, through a specific application of the EDC website, with 1: 1
allocation (stratified by age <60 /> = 60 years old and gender, in blocks of variable size,
random of 4 and 6 units) between placebo and mesoglycan. It is estimated that enrollment was
completed in 24 months.
Scheduled visits: check-ups at 3, 6, 9, 12 months during treatment and at 24 months with:
- overall clinical evaluation and treatment compliance,
- collection of information on any thromboembolic events and / or adverse events,
- evaluation of rVCSS and VEINES / Sym-QoL scores,
- at 12 months, CCDU and blood sampling for complete blood counts, ALT, AST, creatinine,
PT-INR, aPTT and PCR.
- at 24 months, blood sampling for complete blood counts, ALT, AST, creatinine, PT-INR,
aPTT and PCR.
The subject will be instructed to be present at any time for a clinical check in case of
signs / symptoms suggestive of thromboembolic events.
During the treatment period on days: 30, 60, 135, 225, 315 (+ -5 days) from the
randomization, and in the follow-up period after 3, 6 and 9 months from the end of the
treatment and then every 6 months until the end of the study, the subjects will be contacted
by telephone by trained personnel to assess their compliance with treatment, the possible use
of drugs not allowed and the onset of adverse events and / or end-points of the study.
The concomitant use of oral or parenteral anticoagulants, phlebotropics, NSAIDs in chronic
and continuous treatment (except for the occasional symptomatic use of NSAIDs),
double-anti-aggregation or ASA> 160 mg / day, centrally acting painkillers is not permitted
during the study.
The contemporary use of elasto-compressive therapy, of which there is no evidence of real
effectiveness, is left to the clinician's judgment.
Participants will exit permanently from the study if it occurs: one of the primary
end-points, the onset of one of the exclusion criteria, a serious adverse event (SAE) that
achieves one of the exclusion criteria, the withdrawal of consent.
Evaluation criteria:
Primary efficacy end-point: Cumulative occurrence of the first event, with instrumental
confirmation, occurring during the study treatment between: recurrence or extension of,
asymptomatic or symptomatic, SVT, new DVT (proximal asymptomatic or symptomatic / symptomatic
isolated distal), pulmonary embolism (fatal or symptomatic non-fatal).
Secondary efficacy end-points: Cumulative occurrence of the first event between: recurrence
or extension of, asymptomatic or symptomatic, SVT, new proximal / distal DVT (asymptomatic or
symptomatic), pulmonary embolism (fatal or symptomatic non-fatal); modification of the rVCSS
score (efficacy) and VEINES / Sym-QoL (quality of life) in treatment and in the following 12
months; recanalization of the vein involved in the primary thrombotic event; new development
of deep and / or superficial venous reflux; impact of elasto-compressive therapy;
contribution of PCR levels in predicting the onset of the primary end-point.
Security End-Point: Serious adverse events, Total adverse events. Hemorrhagic AEs are
classified as major or minor (ISTH Guidelines).
A copy of the Diagnostic Report of the first event considered will be compulsorily collected
and transmitted to the coordinating center for the validation of the event.
