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Trial · Interventional

Not yet recruitingPhase 2/3Registry data

Intravenous Methylene Blue for Treating Refractory Neonatal Septic Shock

NCTNCT06306001 (opens ClinicalTrials.gov in a new tab)Other idIIRP-2023-1820/F1
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Not yet recruiting
Phase
Phase 2/3
Enrollment
130 participants (estimated)
Sponsor
Post Graduate Institute of Medical Education and Research, Chandigarh · Other
Design
Randomized · Triple masking
Countries
1 country

India

Start
15 Mar 2024 (estimated)
Primary completion
14 Mar 2026 (estimated)
Completion
Feb 2027 (estimated)
First posted
12 Mar 2024
Last update posted
12 Mar 2024
Conditions
Neonatal Sepsis · Shock, Septic

Timeline

1 trial · 1 not yet recruiting

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20242025202620272028
  1. Ph 2/3

    Intravenous Methylene Blue for Treating Refractory Neonatal Septic Shock

    NCT06306001

    est. 15 Mar 2024 to est. Feb 2027

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Preterm infants (born at less than 37 weeks of pregnancy) sometimes develop a serious blood infection leading to low blood pressure, which does not respond to saline or to the standard medicines for increasing blood pressure, such as dopamine and epinephrine. The goal of this research study is to compare the effect of giving an injectable medicine called Methylene blue (MB) versus not giving MB to such preterm infants who are unresponsive to standard treatment. The main questions that this study aims to answer is: 1. Whether MB treatment reduces death to any cause as compared to no MB treatment. 2. Whether treatment with MB reduces the time to achieve normal blood pressure 3. Whether treatment with MB reduces the time to stoppage of all blood pressure medications, steroids and normal saline. 4. Whether treatment with MB improves heart function as measured by echocardiography at 24 and 48 hours.

Interventions

  • Methylene BlueDrug
  • PlaceboOther

Arms2

  • Experimental

    Methylene blue

    Subjects in the intervention arm will receive a 1 mg/kg bolus of methylene blue over 30 minutes, followed by an infusion of 0.15 mg/kg/h. The infusion rate may be increased in steps of 0.15 mg/kg/h every 30 minutes until a maximum of 0.5 mg/kg/h.

  • Placebo comparator

    Placebo infusion

    Subjects in the control arm will receive a placebo infusion (normal saline) at the same volumetric rate.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. All-cause mortality within 7 days after randomization

    Time frame · 7 days

    Registry description

    Mortality due to any cause over 7 days after randomization

Secondary outcomes(16)

  1. Time taken to achieve therapeutic end-points within 7 days after randomization

    Time frame · 7 days

    Registry description

    Time taken to achieve therapeutic end points of shock (which include capillary refill time less than 3 seconds, normal volume pulses, warm extremities, urine output greater than 1 ml/kg/h, normal sensorium, normal mean blood pressure, normal systolic blood pressure and normal diastolic blood pressure) up to 7 days after randomization.

  2. Time taken to stop all inotrope/vasopressor treatment within 7 days after randomisation

    Time frame · 7 days

    Registry description

    Time taken for all inotrope and vasopressor therapy to finally stop up to a maximum of 7 days after randomisation

  3. Echocardiographic fractional shortening at 24 hour after randomization

    Time frame · 24 hour

    Registry description

    Fractional shortening will be calculated on echocardiography by measuring the percentage change in the left ventricular diameter during systole at 24 hours after randomization.

  4. Left ventricular end-diastolic diameter (LVEDD) by echocardiography at 24 hour after randomization

    Time frame · 24 hour

    Registry description

    Left ventricular end-diastolic diameter (LVEDD) will be measured in millimetres by echocardiography at 24 hour after randomization

  5. Left ventricular end-systolic diameter (LVESD) by echocardiography at 24 hour after randomization

    Time frame · 24 hour

    Registry description

    Left ventricular end-systolic diameter (LVESD) will be measured in millimeters by echocardiography at 24 hour after randomization

  6. Aortic diameter by echocardiography at 24 hour after randomization

    Time frame · 24 hour

    Registry description

    Aortic diameter will be measured in millimeters by echocardiography at 24 hour after randomization

  7. Velocity time integral (LVI) by echocardiography at 24 hours after randomization

    Time frame · 24 hour

    Registry description

    Velocity time integral (LVI) will be measured in centimeters by echocardiography at 24 hours after randomization to calculate the cardiac output.

  8. Echocardiographic fractional shortening at 48 hour after randomization

    Time frame · 48 hour

    Registry description

    Fractional shortening will be calculated on echocardiography by measuring the percentage change in the left ventricular diameter during systole at 48 hours after randomization.

  9. Left ventricular end-diastolic diameter (LVEDD) on echocardiography at 48 hour after randomization

    Time frame · 48 hour

    Registry description

    Left ventricular end-diastolic diameter (LVEDD) will be measured in millimeters by echocardiography at 48 hour after randomization

  10. Left ventricular end-systolic diameter (LVESD) by echocardiography at 48 hour after randomization

    Time frame · 48 hour

    Registry description

    Left ventricular end-systolic diameter (LVESD) will be measured in millimeters by echocardiography at 48 hour after randomization

  11. Aortic diameter by echocardiography at 48 hour after randomization

    Time frame · 48 hour

    Registry description

    Aortic diameter will be measured in millimeters by echocardiography at 48 hour after randomization

  12. Velocity time integral (LVI) by echocardiography at 48 hours after randomization

    Time frame · 48 hour

    Registry description

    Velocity time integral (LVI) be measured by echocardiography in centimeters at 48 hours after randomization to calculate the cardiac output.

  13. Time taken to stop vasopressor treatment

    Time frame · 100 days

    Registry description

    Time taken to stop all vasopressors during hospital stay up to a maximum of 100 days

  14. Mortality during hospital stay

    Time frame · 100 days

    Registry description

    Mortality during the period of hospital stay up to a maximum of 100 days

  15. Serious adverse effects

    Time frame · 100 days

    Registry description

    Serious adverse effect with special reference to oliguria, gastrointestinal bleeds, abdominal distension, and bluish discoloration of skin and urine during hospital stay up to a maximum of 100 days

  16. Septic shock-related mortality

    Time frame · 7 days

    Registry description

    Mortality attributed to septic shock up to 7 days post-randomisation

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies10

Studies that cite this trial.

Studies with results

3 studies on this page

Indexing hint: Randomized controlled trial · 2023

7 results

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.

Ibarra-Estrada et al. 2023Critical care (London, England)cited by 69

PMID 36915146PMC10010212DOI 10.1186/s13054-023-04397-7PUB-36915146

CC BY7 results
Download PDFSee results (7)

Indexing hint: Randomized controlled trial · 2004

2 results

Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery.

Levin et al. 2004The Annals of thoracic surgerycited by 191

PMID 14759425DOI 10.1016/s0003-4975(03)01510-8PUB-14759425

Full text at the publisher2 results
Publisher pageSee results (2)

Indexing hint: Randomized controlled trial · 2001

16 results

Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study.

Kirov et al. 2001Critical care medicinecited by 173

PMID 11588440DOI 10.1097/00003246-200110000-00002PUB-11588440

Full text at the publisher16 results
Publisher pageSee results (16)

More studies

7 studies on this page

PubMed tag: none · 2023

Effect of methylene blue on hemodynamic response in the early phase of septic shock: A case series.

Luis-Silva et al. 2023Medicinecited by 7

PMID 36705345PMC9875988DOI 10.1097/md.0000000000032743PUB-36705345

CC BY
Download PDF

Indexing hint: Randomized controlled trial · 2022

Methylene blue versus vasopressin analog for refractory septic shock in the preterm neonate: A randomized controlled trial.

Ismail et al. 2022Journal of neonatal-perinatal medicinecited by 7

PMID 34719443DOI 10.3233/npm-210824PUB-34719443

Full text at the publisher
Publisher page

Indexing hint: Systematic review · 2022

Efficacy and safety of methylene blue in patients with vasodilatory shock: A systematic review and meta-analysis.

Zhao et al. 2022Frontiers in medicinecited by 18

PMID 36237547PMC9552293DOI 10.3389/fmed.2022.950596PUB-36237547

CC BY
Download PDF

Indexing hint: Systematic review · 2020

Methylene Blue for Refractory Shock in Children: A Systematic Review and Survey Practice Analysis.

Otero Luna et al. 2020Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societiescited by 11

PMID 32453920PMC10563197DOI 10.1097/pcc.0000000000002295PUB-32453920

Rights unknown
Source link

Indexing hint: Meta-analysis (pooled) · 2017

[Methylene blue in the treatment of vasodilatory shock: a Meta-analysis].

Zhang et al. 2017Zhonghua wei zhong bing ji jiu yi xuecited by 7

PMID 29151412DOI 10.3760/cma.j.issn.2095-4352.2017.11.005PUB-29151412

Full text at the publisher
Publisher page

Indexing hint: Case report · 2011

Prolonged methylene blue infusion in refractory septic shock: a case report.

Dumbarton et al. 2011Canadian journal of anaesthesia = Journal canadien d'anesthesiecited by 13

PMID 21246318DOI 10.1007/s12630-011-9458-xPUB-21246318

Rights unknown
Source link

Indexing hint: Observational study · 2005

The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock.

Park et al. 2005The Korean journal of internal medicinecited by 37

PMID 16134766PMC3891380DOI 10.3904/kjim.2005.20.2.123PUB-16134766

Free to read · publisher termsCC BY-NC
Read at source

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • ResultHotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available. PMID 12519925
  • ResultStolk RF, Kox M, Pickkers P. Noradrenaline drives immunosuppression in sepsis: clinical consequences. Intensive Care Med. 2020 Jun;46(6):1246-1248. doi: 10.1007/s00134-020-06025-2. Epub 2020 Apr 8. No abstract available. PMID 32270211
  • ResultStolk RF, van der Pasch E, Naumann F, Schouwstra J, Bressers S, van Herwaarden AE, Gerretsen J, Schambergen R, Ruth MM, van der Hoeven JG, van Leeuwen H, Pickkers P, Kox M. Norepinephrine Dysregulates the Immune Response and Compromises Host Defense during Sepsis. Am J Respir Crit Care Med. 2020 Sep 15;202(6):830-842. doi: 10.1164/rccm.202002-0339OC. PMID 32520577
  • ResultMemis D, Karamanlioglu B, Yuksel M, Gemlik I, Pamukcu Z. The influence of methylene blue infusion on cytokine levels during severe sepsis. Anaesth Intensive Care. 2002 Dec;30(6):755-62. doi: 10.1177/0310057X0203000606. PMID 12500513
  • ResultFleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med. 2018 Mar;6(3):223-230. doi: 10.1016/S2213-2600(18)30063-8. PMID 29508706
  • ResultBentzer P, Griesdale DE, Boyd J, MacLean K, Sirounis D, Ayas NT. Will This Hemodynamically Unstable Patient Respond to a Bolus of Intravenous Fluids? JAMA. 2016 Sep 27;316(12):1298-309. doi: 10.1001/jama.2016.12310. PMID 27673307
  • ResultAya HD, Ster IC, Fletcher N, Grounds RM, Rhodes A, Cecconi M. Pharmacodynamic Analysis of a Fluid Challenge. Crit Care Med. 2016 May;44(5):880-91. doi: 10.1097/CCM.0000000000001517. PMID 26683506
  • ResultNandhabalan P, Ioannou N, Meadows C, Wyncoll D. Refractory septic shock: our pragmatic approach. Crit Care. 2018 Sep 19;22(1):215. doi: 10.1186/s13054-018-2144-4. PMID 30231909
  • ResultEvora PR, Roselino CH, Schiaveto PM. Methylene blue in anaphylactic shock. Ann Emerg Med. 1997 Aug;30(2):240. doi: 10.1016/s0196-0644(97)70152-5. No abstract available. PMID 9250657
  • ResultKudawla M, Dutta S, Narang A. Validation of a clinical score for the diagnosis of late onset neonatal septicemia in babies weighing 1000-2500 g. J Trop Pediatr. 2008 Feb;54(1):66-9. doi: 10.1093/tropej/fmm065. Epub 2007 Aug 14. PMID 17698886

Eligibility

Who could join, as posted.

Sex
All
Age
from 0 Days up to 28 Days
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Screening Criteria: preterm infants (\<37 weeks, \<28 days) clinically diagnosed to have septic shock will be screened for inclusion Inclusion criteria: Subjects must fulfill all the following 1. Definite/probable sepsis :Clinical syndrome of sepsis for which bedside neonatologist starts intravenous antibiotics AND either a positive culture of otherwise sterile body fluid OR presence of any 2 or more of the following five markers of sepsis: (a) C-reactive protein \>10 mg/dL; (b) procalcitonin as per age-appropriate cut-off (c) total leukocyte count and absolute neutrophilic count beyond acceptable range (d) chest X-ray adjudged as pneumonia by two independent Neonatologists. 2. Shock: adapted from the definition given by Davis et al 2017 1. Either SBP \< age and gestation appropriate cut-off OR 2. Presence of any 2 of the following 6 parameters i. HR \>205/min ii. Central pulses either week OR bounding iii. CRT \>3 sec OR flash refill (\<1 sec) iv. skin mottled/cool OR flushed v. urine output \<0.5 ml/kg/h in the preceding 6 hours vi. DBP \< age and gestation appropriate cut-off 3. Fluid and catecholamine-resistant shock: received fluid boluses up to a maximum of 40 ml/kg followed by catecholamine infusion titrated up to the maximum dose. The catecholamine infusion could be either dopamine (maximum dose 20 µg/kg/min) or epinephrine (maximum dose 0.4 µg/kg/min) or norepinephrine (maximum dose 0.4 µg/kg/min). Exclusion Criteria: excluded if ≥1 criterion positive: 1. G6PD deficient or family history of G6PD deficiency 2. Potentially lethal malformation 3. Congenital heart disease 4. Severe acute kidney injury 5. Family history of allergy to methylene blue or food dyes

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