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

December 4, 2025 updated by: University Hospital Ostrava

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
    • Moravian-Silesian Region
      • Ostrava, Moravian-Silesian Region, Czechia, 708 52
        • University Hospital Ostrava

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Manual Lymphatic Drainage
In addition to usual care, daily manual lymphatic drainage will be performed for five consecutive days. After this period.
Procedure: Manual Lymphatic Drainage
Manual lymphatic drainage massage involves gently manipulating specific areas of the body to help lymph move to an area with working lymph vessels.
Active Comparator: Usual Care
Usual care for patients with septic shock will be provided.
Procedure: Usual Care
Usual care provided for patients in septic shock.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility Outcome - number of patients undergoing manual lymphatic drainage procedure.
Time Frame: 12 months
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.
Time Frame: 12 months
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
Time Frame: 12 months
interference is assumed in 0 per cent of cases
12 months
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
12 months
Safety Outcome - incidence of thromboembolic events
Time Frame: 12 months
The presumed incidence is assumed in 0 per cent of cases
12 months
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)
12 months
Efficacy Outcome - incidence of delirium
Time Frame: 12 months
Incidence of delirium for the period from randomisation until discharge from ICU
12 months
Efficacy Outcome - 28-day mortality
Time Frame: 12 months
28-day mortality will be observed
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Ostrava

Investigators

  • Principal Investigator: Roman Kula, MD,CSc, University Hospital Ostrava

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2023

Primary Completion (Actual)

May 31, 2024

Study Completion (Actual)

November 28, 2025

Study Registration Dates

First Submitted

May 11, 2023

First Submitted That Met QC Criteria

May 22, 2023

First Posted (Actual)

May 25, 2023

Study Record Updates

Last Update Posted (Actual)

December 12, 2025

Last Update Submitted That Met QC Criteria

December 4, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MADAME trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to make individual participant data available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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