MAnual Lymphatic DrAinage to iMprove the outcomE of Patients After Septic Shock

NCT05874895 | Completed

• 1 other identifier: MADAME trial
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Sepsis; Multiorgan Failure; Inflammatory Response; Septic Shock

Keywords

Sepsis; Multiorgan Failure; Excessive Inflammatory Response; Manual Lymphatic Drainage; Lymphatic System; Septic Shock

Outcome Measures

Primary Outcomes (8)

• Feasibility Outcome - number of patients undergoing manual lymphatic drainage procedure.

  The anticipated number of patients is 2 per month.

  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.

  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

  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

  12 months

• Safety Outcome - incidence of thromboembolic events

  The presumed incidence is assumed in 0 per cent of cases

  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)

  12 months

• Efficacy Outcome - incidence of delirium

  Incidence of delirium for the period from randomisation until discharge from ICU

  12 months

• Efficacy Outcome - 28-day mortality

  28-day mortality will be observed

  12 months

Study Arms (2)

Manual Lymphatic Drainage

EXPERIMENTAL

In addition to usual care, daily manual lymphatic drainage will be performed for five consecutive days. After this period.

Procedure: Manual Lymphatic Drainage

Usual Care

ACTIVE COMPARATOR

Usual care for patients with septic shock will be provided.

Procedure: Usual Care

Interventions

Manual Lymphatic Drainage PROCEDURE

Manual lymphatic drainage massage involves gently manipulating specific areas of the body to help lymph move to an area with working lymph vessels.

Manual Lymphatic Drainage

Usual Care PROCEDURE

Usual care provided for patients in septic shock.

Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

• University Hospital Ostrava: lead

Study Sites (1)

University Hospital Ostrava

Ostrava, Moravian-Silesian Region, 708 52, Czechia

Location

Related Publications (13)

• Alitalo K. The lymphatic vasculature in disease. Nat Med. 2011 Nov 7;17(11):1371-80. doi: 10.1038/nm.2545.

  PMID: 22064427 BACKGROUND

• Venero 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.

  PMID: 27576003 BACKGROUND

• Oliver 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.

  PMID: 32707093 BACKGROUND

• Vairo 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.

  PMID: 20046617 BACKGROUND

• Scallan 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.

  PMID: 27219461 BACKGROUND

• Klaourakis 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.

  PMID: 33462421 BACKGROUND

• Pruitt 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.

  PMID: 32339860 BACKGROUND

• Vieira 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.

  PMID: 29985167 BACKGROUND

• Frohlich 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.

  PMID: 34829961 BACKGROUND

• Schwager S, Detmar M. Inflammation and Lymphatic Function. Front Immunol. 2019 Feb 26;10:308. doi: 10.3389/fimmu.2019.00308. eCollection 2019.

  PMID: 30863410 BACKGROUND

• Kraft 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.

  PMID: 33803130 BACKGROUND

• Fanous MY, Phillips AJ, Windsor JA. Mesenteric lymph: the bridge to future management of critical illness. JOP. 2007 Jul 9;8(4):374-99.

  PMID: 17625290 BACKGROUND

• Wu 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.

  PMID: 33262632 BACKGROUND

MeSH Terms

Conditions

Sepsis; Multiple Organ Failure; Shock, Septic

Interventions

Manual Lymphatic Drainage

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Massage; Therapy, Soft Tissue; Musculoskeletal Manipulations; Complementary Therapies; Therapeutics; Drainage; Physical Therapy Modalities; Rehabilitation

Study Officials

• Roman Kula, MD,CSc

  University Hospital Ostrava

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking will be used in this study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study subjects will be randomized in two study arms.

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: May 25, 2023
• Study Start: June 1, 2023
• Primary Completion: May 31, 2024
• Study Completion: November 28, 2025
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)