Treatment of Congenital Vascular Malformations Using Sirolimus: Improving Quality of Life (Sirolimus)
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|ClinicalTrials.gov Identifier: NCT03987152|
Recruitment Status : Unknown
Verified October 2020 by Radboud University Medical Center.
Recruitment status was: Active, not recruiting
First Posted : June 14, 2019
Last Update Posted : January 29, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Vascular Malformations||Drug: Sirolimus||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Challenge-Dechallenge-Rechallenge design All patients receive Sirolimus during challenge phase (6 months), stop Sirolimus during dechallenge phase (12 months), and if pain/symptoms returns Sirolimus intake is restarted during the rechallenge phase.|
|Masking:||None (Open Label)|
|Official Title:||Treatment of Congenital Vascular Malformations Using Sirolimus: Improving Quality of Life|
|Actual Study Start Date :||September 18, 2017|
|Estimated Primary Completion Date :||September 18, 2021|
|Estimated Study Completion Date :||March 1, 2023|
Sirolimus administration: during Challenge and Rechallenge phase. Compared with the period 2 months before start of Sirolimus.
Daily intake of Sirolimus during Challenge and Rechallenge phase
Other Name: No other treatment
- Quality of life using Sirolimus measured with survey (TAPQOL) [ Time Frame: Change from baseline Quality of life at 6 months QoL in challenge phase, and 12 months QoL in Rechallenge phase. ]Quality of life: Questionnaire for Preschool Children's Health-Related Quality of Life (TAPQOL). Preschool Children Quality of Life, parent-reported questionnaire clustered into 12 multi-item scales, with higher scores range 0-100) indicating better HRQOL)
- Quality of life using Sirolimus measured with survey (PedsQl) [ Time Frame: Change from baseline Quality of life at 6 months QoL in challenge phase, and 12 months QoL in Rechallenge phase. ]Quality of life: Pediatric Quality of Life Inventory (PedsQl) (children) 23 items questionnaire, 0-100 scale, so that higher scores indicate better HRQOL (Health-Related Quality of Life). Psychosocial Health Summary Score, Physical Health Summary Score and Total score will be measured.
- Quality of life using Sirolimus measured with survey (Research and development Rand-36). [ Time Frame: hange from baseline Quality of life at 6 months QoL in challenge phase, and 12 months QoL in Rechallenge phase ]Quality of life: Rand-36 (adults) eight health domains; physical functioning, social functioning, role limitations due to physical health problems, role limitations due to emotional problems, mental health, vitality, pain and general health perception. Outcomes at each domain will be defined on a scale from a minimum score of 0 to a maximum score of 100. A higher score is equivalent to a better health.
- Difference in pain scores after using Sirolimus measured with VAS score [ Time Frame: Daily pain scores will be compared after 6 months in Challenge phase, after Challenge phase: starts the phase, and pain during 12 months in the Rechallenge phase ]Daily pain score (daily visual analogue scale (VAS-score 0-10) for children, and numeric rating scale (NRS-score 0-10) for adults)
- Difference in pain scores after using Sirolimus measured with NRS score [ Time Frame: Daily pain scores will be compared after 6 months in Challenge phase, after Challenge phase: starts the phase without Sirolimus treatment, and pain during 12 months in the Rechallenge phase ]Daily pain score (daily numeric rating scale (NRS-score 0 no pain -10 extreme pain) for adults)
- Return of pain after treatment and duration of lowered pain or pain free period in days [ Time Frame: After 6 months Sirolimus intake till one year follow up. ]Amount of patients who have lowered pain or are pain free. Duration of lowered pain or pain free period in days.
- Growth/progression of vascular malformation [ Time Frame: MRI baseline compared with MRI after 6 months in challenge phase and 12 months in rechallenge phase ]MRI of the vascular malformation will be made at the beginning of the study and after six months of treatment with Sirolimus. An experienced radiologist will evaluate the evolution of the volume of the malformation.
- Rate and occurence of adverse events related to Sirolimus [ Time Frame: 4 years ]Adverse events: short and long term consequences of treatment with Sirolimus according to CTCAE version 5.0.
- Severity of adverse events related to Sirolimus [ Time Frame: 4 years ]Adverse events: short and long term consequences of treatment with Sirolimus according to CTCAE version 5.0.
- Genetic mutations in the vascular malformation that can predict outcome of treatment with Sirolimus using Single Molecule Molecular Inversion Probes (smMIPs) [ Time Frame: 4 years ]Secondary material that was obtained after surgery, stored in the HECOVAN biobank can be used for analyses. Comprehensive targeted Next Generation Sequencing screen using Unique Molecular Identifiers with a technical sensitivity of 1% mutant alleles was performed for frequently mutated positions using Single Molecule Molecular Inversion Probes. We will investigate if there is a correlation with a possible found mutation and painreduction or improvement of quality of life.
- Pharmacogenetic profile in the vascular malformation that can predict outcome of treatment with Sirolimus [ Time Frame: 4 years ]Genotyping will be performed using Taqman assays or Kompetitive Allele Specific PCR (KASPTM) assays in saliva swabs. Pharmacogenetic profiles (slow, intermediate, and extensive metabolizer) will be determined. Subjects compared on the outcome of sirolimus effectiveness for pain, and QoL stratified by CYP3A4.
- Cost-effectiveness of administration of Sirolimus: Quality Adjusted Life Year (QALY) estimate for each patient [ Time Frame: 4 years ]Via standardized questionnaires developed by the iMTA (institute for Medical Technology Assessment). The second part of the cost analysis consists of determining the cost prices for each volume of consumption.
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|Ages Eligible for Study:||1 Year and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Diagnosis of Congenital venous malformation, or lymphatic malformation or combined.
- Age older than 1 yr.
- Patients (or legal guardians for children) have to be able to sign the informed consent
- Patients are either refractory to standard care such as medical treatment (low molecular weight heparins, pain medication etc.), surgical resection and/or sclerotherapy/embolization (ineffective or accompanied by major complications) or there is no possibility for surgical intervention anymore. Only patients that have a normal clinical screening (no signs for infection, normal bone marrow function, normal liver and kidney function, normal glucose metabolism etc.) can be included.
- Patients included have no cardiac impairment
- Patients have no gastrointestinal impairment as Sirolimus is absorbed gastro-intestinal and normal function is needed
- No other underlying medical disorder like Down syndrome or other syndromes
- Women of reproductive age have to be informed that contraceptive methods are
- mandatory during the study time, pregnant women are excluded
- Karnofsky score > 50
- No written informed consent
- Known hypersensitivity to drugs or metabolites from similar classes as study treatment.
- Patient has other concurrent severe and /or uncontrolled medical condition that would, in the investigator's judgment, contraindicated participation in the clinical study (e.g. acute or chronic pancreatitis, liver cirrhosis, active chronic hepatitis, severely impaired lung function with a spirometry ≤ 50% of the normal predicted value and/or O2 saturation ≤ 88% at rest, etc.)
- Recent history of primary malignancy ≤ 5 years
- Impaired cardiac function or clinically significant cardiac diseases
- Immunocompromised patients, including known seropositivity for HIV
- Patient with any other concurrent severe and /or uncontrolled medical condition that would,in the investigator's judgment, contraindicated participation in the clinical study.
- Pregnant or lactating women
- Karnofsky score < 50
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03987152
|Radboudumc, HECOVAN workgroup|
|Nijmegen, Gelderland, Netherlands, 6500HB|
|Principal Investigator:||Maroeska Loo, te, Dr.||Radboud University Medical Center|
|Responsible Party:||Radboud University Medical Center|
|Other Study ID Numbers:||
2016-002157-38 ( EudraCT Number )
|First Posted:||June 14, 2019 Key Record Dates|
|Last Update Posted:||January 29, 2021|
|Last Verified:||October 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Quality of life
mammalian target of rapamycin (mTOR)
Physiological Effects of Drugs