SepsisMADAMENCT05874895
MAnual Lymphatic DrAinage to iMprove the outcomE of Patients After Septic Shock
A study testing Manual Lymphatic Drainage in people with Sepsis and Multiorgan Failure, run by University Hospital Ostrava at 1 site in Czechia.
Trial summary
Antimicrobial and supportive therapeutic interventions in patients with septic shock are usually effective - procalcitonin and interleukin-6 levels fall rapidly in most cases, and noradrenaline support can be discontinued within a few days. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Multiorgan Failure, Inflammatory Response
- What is being tested?
- Manual Lymphatic Drainage
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCzechia
- Study dates
- 1 Jun 2023to 28 Nov 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosis of septic shock at admission to ICU
- sepsis or suspicion of sepsis
- noradrenaline support required in order to maintain mean arterial pressure ≥ 65 mmHg
- serum lactate ≥ 2 mmol/L
Who cannot join
- patients <18 years of age
- pregnant women with septic shock, in whom the pregnancy has been preserved
- patients with a history of heart failure with NYHA (New York Heart Association) classification ≥ III
- patients with a history of thromboembolic events
- patients with septic shock transferred from another department/hospital, if the length of stay at the previous workplace exceeded 72 hours
- patients with septic shock and an inauspicious prognosis, or in the phase of withdrawal of treatment
Show all 9Show fewer
- patients with uncontrolled infection
- patients with septic shock who lack informed consent
- patients with septic shock, in whom the SOFA score decreased by more than 50% during the day following the withdrawal of noradrenaline (i.e. a subgroup of patients with a rapid improvement of the clinical course after the resolution of septic shock).
Trial locations and contacts
1 site in 1 country.
Czechia1 site
University Hospital Ostrava
Ostrava, Moravian-Silesian Region, 708 52
About this study
Official title: MAnual Lymphatic DrAinage to iMprove the outcomE of Patients After Septic Shock: A Safety and Feasibility Pilot Randomized Controlled Trial
Antimicrobial and supportive therapeutic interventions in patients with septic shock are usually effective - procalcitonin and interleukin-6 levels fall rapidly in most cases, and noradrenaline support can be discontinued within a few days. Unfortunately, only in a small portion of patients, do the organ functions improve at the same time, and in most of them, multi-organ failure persists. Therefore, it is likely that, in addition to infection and the response to infection, other mechanisms are also involved in the persistence of organ failure in patients after septic shock.
Read the detailed description
One of the possible explanations for prolonged multi-organ dysfunction after an excessive inflammatory phase is a disorder of "post-inflammatory cleaning", the so-called resolution of inflammation. The resolution of inflammation is a regulated process in which the controlling action of specialized pro-resolution mediators (lipoxins, resolvins, etc.), conversion of pro-inflammatory macrophages (M1) to pro-resolution (M2., induce the process of structural tissue restoration), autophagy plays a significant role and, of course, the flushing of accumulated interstitial fluid with waste products by lymphatic drainage. Any disturbance in pro-resolution mechanisms can lead to prolonged organ dysfunction.
The lymphatic system plays a key role in maintaining fluid homeostasis. Its ability to drain interstitial fluid can increase up to 20 times. However, even such an increase may not be sufficient in the situation of extreme interstitial fluid sequestration that accompanies septic shock. In addition, some inflammatory mediators (for example, nitric oxide, TNF-α, Interleukin-1β) cause relaxation of the vascular structures of the lymphatic system, slowing the flow of lymph. The result is the persistence of tissue swelling with tissue hypoxia due to the extension of the diffusion path for oxygen and the accumulation of waste products of inflammation.
Manual lymphatic drainage (MLD) is one of the treatments that stimulate the lymphatic system. In general, it is expected to accelerate the outflow of lymph and waste products from tissues previously affected by inflammation, accelerate the recovery of tissue function, sympatholytic effect and increase the tension of the vagus nerve. It can therefore be assumed that MLD will have a beneficial effect on the course of persistent multi-organ dysfunction in patients after therapeutically managed septic shock.
- Conditions
- Sepsis, Multiorgan Failure, Inflammatory Response, Septic Shock
- Being tested
- Manual Lymphatic Drainage, Usual Care
- Keywords
- Sepsis, Multiorgan Failure, Excessive Inflammatory Response, Manual Lymphatic Drainage, Lymphatic System, Septic Shock
- Medical subject headings
- Sepsis, Multiple Organ Failure, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Manual Lymphatic DrainageProcedure or surgery
Manual lymphatic drainage massage involves gently manipulating specific areas of the body to help lymph move to an area with working lymph vessels.
Usual CareProcedure or surgery
Usual care provided for patients in septic shock.
| Study group | Role | What they receive |
|---|---|---|
| Manual Lymphatic Drainage | Experimental | In addition to usual care, daily manual lymphatic drainage will be performed for five consecutive days. After this period. Receives: Procedure: Manual Lymphatic Drainage |
| Usual Care | Active comparator | Usual care for patients with septic shock will be provided. Receives: Procedure: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility Outcome - number of patients undergoing manual lymphatic drainage procedure.
The anticipated number of patients is 2 per month.
Measured: 12 months
Feasibility Outcome - The percentage of patients suitable for manual lymphatic drainage procedure in whom this procedure has been performed.
It is expected that manual lymphatic drainage procedure will be performed in at least 80 per cent of patients.
Measured: 12 months
Safety Outcome - the percentage of cases when the manual lymphatic drainage procedure interferes with standard nursing care
interference is assumed in 0 per cent of cases
Measured: 12 months
Safety Outcome - incidence of the need to restart circulatory support with norepinephrine
The presumed incidence is assumed in 0 per cent of cases
Measured: 12 months
Safety Outcome - incidence of thromboembolic events
The presumed incidence is assumed in 0 per cent of cases
Measured: 12 months
Efficacy Outcome - change in SOFA (sequential organ failure assessment) score
Comparison of the SOFA score on Days 3 and 5 versus Day 0 (randomisation day)
Measured: 12 months
Efficacy Outcome - incidence of delirium
Incidence of delirium for the period from randomisation until discharge from ICU
Measured: 12 months
Efficacy Outcome - 28-day mortality
28-day mortality will be observed
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2023
- Study start1 Jun 2023
- Primary completion31 May 2024
- Study completion28 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study subjects will be randomized in two study arms.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Ostrava
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roman Kula, MD,CSc, Principal investigator, University Hospital Ostrava
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05874895
- Sponsor's protocol ID
- MADAME trial
- Acronym
- MADAME
- Status last verified
- Dec 2025
- First submitted
- 11 May 2023
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make individual participant data available to other researchers.
Publications
Alitalo K. The lymphatic vasculature in disease. Nat Med. 2011 Nov 7;17(11):1371-80. doi: 10.1038/nm.2545.
PubMed 22064427Venero Galanternik M, Stratman AN, Jung HM, Butler MG, Weinstein BM. Building the drains: the lymphatic vasculature in health and disease. Wiley Interdiscip Rev Dev Biol. 2016 Nov;5(6):689-710. doi: 10.1002/wdev.246. Epub 2016 Aug 30.
PubMed 27576003Oliver G, Kipnis J, Randolph GJ, Harvey NL. The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease. Cell. 2020 Jul 23;182(2):270-296. doi: 10.1016/j.cell.2020.06.039.
PubMed 32707093Vairo GL, Miller SJ, McBrier NM, Buckley WE. Systematic review of efficacy for manual lymphatic drainage techniques in sports medicine and rehabilitation: an evidence-based practice approach. J Man Manip Ther. 2009;17(3):e80-9. doi: 10.1179/jmt.2009.17.3.80E.
PubMed 20046617Scallan JP, Zawieja SD, Castorena-Gonzalez JA, Davis MJ. Lymphatic pumping: mechanics, mechanisms and malfunction. J Physiol. 2016 Oct 15;594(20):5749-5768. doi: 10.1113/JP272088. Epub 2016 Aug 2.
PubMed 27219461Klaourakis K, Vieira JM, Riley PR. The evolving cardiac lymphatic vasculature in development, repair and regeneration. Nat Rev Cardiol. 2021 May;18(5):368-379. doi: 10.1038/s41569-020-00489-x. Epub 2021 Jan 18.
PubMed 33462421Pruitt LG. Lymphatic flow modulation as adjunct therapy for septic shock. Med Hypotheses. 2020 Sep;142:109748. doi: 10.1016/j.mehy.2020.109748. Epub 2020 Apr 20.
PubMed 32339860Vieira JM, Norman S, Villa Del Campo C, Cahill TJ, Barnette DN, Gunadasa-Rohling M, Johnson LA, Greaves DR, Carr CA, Jackson DG, Riley PR. The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction. J Clin Invest. 2018 Aug 1;128(8):3402-3412. doi: 10.1172/JCI97192. Epub 2018 Jul 9.
PubMed 29985167Frohlich E. Acute Respiratory Distress Syndrome: Focus on Viral Origin and Role of Pulmonary Lymphatics. Biomedicines. 2021 Nov 20;9(11):1732. doi: 10.3390/biomedicines9111732.
PubMed 34829961Schwager S, Detmar M. Inflammation and Lymphatic Function. Front Immunol. 2019 Feb 26;10:308. doi: 10.3389/fimmu.2019.00308. eCollection 2019.
PubMed 30863410Kraft JD, Blomgran R, Lundgaard I, Quiding-Jarbrink M, Bromberg JS, Borgeson E. Specialized Pro-Resolving Mediators and the Lymphatic System. Int J Mol Sci. 2021 Mar 9;22(5):2750. doi: 10.3390/ijms22052750.
PubMed 33803130Fanous MY, Phillips AJ, Windsor JA. Mesenteric lymph: the bridge to future management of critical illness. JOP. 2007 Jul 9;8(4):374-99.
PubMed 17625290Wu C, Li H, Zhang P, Tian C, Luo J, Zhang W, Bhandari S, Jin S, Hao Y. Lymphatic Flow: A Potential Target in Sepsis-Associated Acute Lung Injury. J Inflamm Res. 2020 Nov 23;13:961-968. doi: 10.2147/JIR.S284090. eCollection 2020.
PubMed 33262632
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MAnual Lymphatic DrAinage to iMprove the outcomE of Patients After Septic Shock: A Safety and Feasibility Pilot Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05874895
- Acronym / sponsor ID
- MADAME / MADAME trial
- Conditions
- Sepsis, Multiorgan Failure, Inflammatory Response, Septic Shock
- Keywords
- Sepsis, Multiorgan Failure, Excessive Inflammatory Response, Manual Lymphatic Drainage, Lymphatic System, Septic Shock
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital OstravaUniversity, hospital or other
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 31 May 2024 (actual)
- Study completion
- 28 Nov 2025 (actual)
- First posted
- 25 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antimicrobial and supportive therapeutic interventions in patients with septic shock are usually effective - procalcitonin and interleukin-6 levels fall rapidly in most cases, and noradrenaline support can be discontinued within a few days. Unfortunately, only in a small portion of patients, do the organ functions improve at the same time, and in most of them, multi-organ failure persists. Therefore, it is likely that, in addition to infection and the response to infection, other mechanisms are also involved in the persistence of organ failure in patients after septic shock.
Detailed description
One of the possible explanations for prolonged multi-organ dysfunction after an excessive inflammatory phase is a disorder of "post-inflammatory cleaning", the so-called resolution of inflammation. The resolution of inflammation is a regulated process in which the controlling action of specialized pro-resolution mediators (lipoxins, resolvins, etc.), conversion of pro-inflammatory macrophages (M1) to pro-resolution (M2., induce the process of structural tissue restoration), autophagy plays a significant role and, of course, the flushing of accumulated interstitial fluid with waste products by lymphatic drainage. Any disturbance in pro-resolution mechanisms can lead to prolonged organ dysfunction.
The lymphatic system plays a key role in maintaining fluid homeostasis. Its ability to drain interstitial fluid can increase up to 20 times. However, even such an increase may not be sufficient in the situation of extreme interstitial fluid sequestration that accompanies septic shock. In addition, some inflammatory mediators (for example, nitric oxide, TNF-α, Interleukin-1β) cause relaxation of the vascular structures of the lymphatic system, slowing the flow of lymph. The result is the persistence of tissue swelling with tissue hypoxia due to the extension of the diffusion path for oxygen and the accumulation of waste products of inflammation.
Manual lymphatic drainage (MLD) is one of the treatments that stimulate the lymphatic system. In general, it is expected to accelerate the outflow of lymph and waste products from tissues previously affected by inflammation, accelerate the recovery of tissue function, sympatholytic effect and increase the tension of the vagus nerve. It can therefore be assumed that MLD will have a beneficial effect on the course of persistent multi-organ dysfunction in patients after therapeutically managed septic shock.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study subjects will be randomized in two study arms.
| Arm | Type | Receives |
|---|---|---|
| Manual Lymphatic Drainage | Experimental | Procedure: Manual Lymphatic DrainageIn addition to usual care, daily manual lymphatic drainage will be performed for five consecutive days. After this period. |
| Usual Care | Active comparator | Procedure: Usual CareUsual care for patients with septic shock will be provided. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- diagnosis of septic shock at admission to ICU
- sepsis or suspicion of sepsis
- noradrenaline support required in order to maintain mean arterial pressure ≥ 65 mmHg
- serum lactate ≥ 2 mmol/L
Key exclusion criteria (9 listed)
- patients <18 years of age
- pregnant women with septic shock, in whom the pregnancy has been preserved
- patients with a history of heart failure with NYHA (New York Heart Association) classification ≥ III
- patients with a history of thromboembolic events
- patients with septic shock transferred from another department/hospital, if the length of stay at the previous workplace exceeded 72 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Manual Lymphatic DrainageManual lymphatic drainage massage involves gently manipulating specific areas of the body to help lymph move to an area with working lymph vessels. | Procedure or surgery | Manual Lymphatic Drainage |
| Usual CareUsual care provided for patients in septic shock. | Procedure or surgery | Usual Care |
Primary outcome
Feasibility Outcome - number of patients undergoing manual lymphatic drainage procedure.
Time frame: 12 months
The anticipated number of patients is 2 per month.
Feasibility Outcome - The percentage of patients suitable for manual lymphatic drainage procedure in whom this procedure has been performed.
Time frame: 12 months
It is expected that manual lymphatic drainage procedure will be performed in at least 80 per cent of patients.
Safety Outcome - the percentage of cases when the manual lymphatic drainage procedure interferes with standard nursing care
Time frame: 12 months
interference is assumed in 0 per cent of cases
Safety Outcome - incidence of the need to restart circulatory support with norepinephrine
Time frame: 12 months
The presumed incidence is assumed in 0 per cent of cases
Safety Outcome - incidence of thromboembolic events
Time frame: 12 months
The presumed incidence is assumed in 0 per cent of cases
Efficacy Outcome - change in SOFA (sequential organ failure assessment) score
Time frame: 12 months
Comparison of the SOFA score on Days 3 and 5 versus Day 0 (randomisation day)
Efficacy Outcome - incidence of delirium
Time frame: 12 months
Incidence of delirium for the period from randomisation until discharge from ICU
Efficacy Outcome - 28-day mortality
Time frame: 12 months
28-day mortality will be observed
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
- Background: PubMed 22064427Alitalo K. The lymphatic vasculature in disease. Nat Med. 2011 Nov 7;17(11):1371-80. doi: 10.1038/nm.2545.
- Background: PubMed 27576003Venero Galanternik M, Stratman AN, Jung HM, Butler MG, Weinstein BM. Building the drains: the lymphatic vasculature in health and disease. Wiley Interdiscip Rev Dev Biol. 2016 Nov;5(6):689-710. doi: 10.1002/wdev.246. Epub 2016 Aug 30.
- Background: PubMed 32707093Oliver G, Kipnis J, Randolph GJ, Harvey NL. The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease. Cell. 2020 Jul 23;182(2):270-296. doi: 10.1016/j.cell.2020.06.039.
- Background: PubMed 20046617Vairo GL, Miller SJ, McBrier NM, Buckley WE. Systematic review of efficacy for manual lymphatic drainage techniques in sports medicine and rehabilitation: an evidence-based practice approach. J Man Manip Ther. 2009;17(3):e80-9. doi: 10.1179/jmt.2009.17.3.80E.
- Background: PubMed 27219461Scallan JP, Zawieja SD, Castorena-Gonzalez JA, Davis MJ. Lymphatic pumping: mechanics, mechanisms and malfunction. J Physiol. 2016 Oct 15;594(20):5749-5768. doi: 10.1113/JP272088. Epub 2016 Aug 2.
- Background: PubMed 33462421Klaourakis K, Vieira JM, Riley PR. The evolving cardiac lymphatic vasculature in development, repair and regeneration. Nat Rev Cardiol. 2021 May;18(5):368-379. doi: 10.1038/s41569-020-00489-x. Epub 2021 Jan 18.
- Background: PubMed 32339860Pruitt LG. Lymphatic flow modulation as adjunct therapy for septic shock. Med Hypotheses. 2020 Sep;142:109748. doi: 10.1016/j.mehy.2020.109748. Epub 2020 Apr 20.
- Background: PubMed 29985167Vieira JM, Norman S, Villa Del Campo C, Cahill TJ, Barnette DN, Gunadasa-Rohling M, Johnson LA, Greaves DR, Carr CA, Jackson DG, Riley PR. The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction. J Clin Invest. 2018 Aug 1;128(8):3402-3412. doi: 10.1172/JCI97192. Epub 2018 Jul 9.
- Background: PubMed 34829961Frohlich E. Acute Respiratory Distress Syndrome: Focus on Viral Origin and Role of Pulmonary Lymphatics. Biomedicines. 2021 Nov 20;9(11):1732. doi: 10.3390/biomedicines9111732.
- Background: PubMed 30863410Schwager S, Detmar M. Inflammation and Lymphatic Function. Front Immunol. 2019 Feb 26;10:308. doi: 10.3389/fimmu.2019.00308. eCollection 2019.
- Background: PubMed 33803130Kraft JD, Blomgran R, Lundgaard I, Quiding-Jarbrink M, Bromberg JS, Borgeson E. Specialized Pro-Resolving Mediators and the Lymphatic System. Int J Mol Sci. 2021 Mar 9;22(5):2750. doi: 10.3390/ijms22052750.
- Background: PubMed 17625290Fanous MY, Phillips AJ, Windsor JA. Mesenteric lymph: the bridge to future management of critical illness. JOP. 2007 Jul 9;8(4):374-99.
- Individual participant dataSharing planned: No. There is no plan to make individual participant data available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roman Kula, MD,CSc principal investigator
University Hospital Ostrava
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Manual Lymphatic Drainage in people with Sepsis and Multiorgan Failure, run by University Hospital Ostrava at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility Outcome - number of patients undergoing manual lymphatic drainage procedure. (time frame: 12 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05874895, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2025.