Patient Blood Management for Massive Obstetric Hemorrhage

NCT03784794 | Completed DMC

• 1 other identifier: 099/21012018/MEDCRITICAHENM
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Obstetric Hemorrhage continues to be the first cause of maternal morbidity and mortality around the world especially in middle to low income countriesThe blood components are high value resources; however, its use has been shown to be a risk factor of known complications. The aim of the study is to compare two algorithms of coagulation management in massive obstetric hemorrhage Methods A randomized prospective trial single center two arms study in patients with severe obstetric hemorrhage (PPH \> 1000) 2 different transfusion protocols one guided by thromboelastometry and hemostatic drugs (protrombine complex concentrate and fibrinogen concentrate) and the second guided by standard coagulation test and hemocomponents. Sample is calculated to known variance, Analyses are intention-to-treat without imputation, with outcomes will be performed between groups using mixed-effects two level regression models. For binary outcomes, a logistic model will be used and results presented as adjusted odds ratios (ORs) alongside 95% confidence intervals (CIs). Count data will be analysed using Poisson multilevel or negative binomial models. Primary Outcome Parameter: Compare between the two protocols: Number of allogeneic blood products transfused intra-op, within 24h after screening and in-hospital (RBC, Platelets and FFP; separate and overall) Secondary Outcome Parameter: Analysis of mortality, lenth of stay admission to the ICU, hysterectomy surgical reintervencion, Transfuse associated circulatory overload, Transfusion associated Acute lung injury, health associated infection will be measured as secondary outcome.

Conditions

Post Partum Hemorrhage; Fibrinogenolysis; Hemorrhage; Fibrinogen; Deficiency, Acquired; Massive Hemorrhage; Transfusion Related Complication

Keywords

Post Partum Hemorrhage; Massive tranfusion; Thromboelastometry

Outcome Measures

Primary Outcomes (1)

• Number of Blood products transfused

  Number of allogeneic blood products transfused intra-op, within 24h after screening and in-hospital (RBC, Platelets and FFP; separate and overall)

  24 hrs

Secondary Outcomes (12)

• Number of hemocomponents or fibrinogen concentrates needed to treat hypofibrinogenemia

  day 0 to day 15

• Incidence of Red Blood Cells transfusion (RBC)

  day 0 to day 15

• Incidence of Massive Red Blood Cells transfusion (RBC)

  day 0 to day 15

• estimated blood loss

  day 0 to day 15

• Time to bleeding control

  24 hrs

Study Arms (2)

Thromboelastometry

EXPERIMENTAL

Decision to treat will be guided with thromboelastometry results, for fribrinogen deficiency the investigators will treat with fibrinogen concentrate (human), for correction of factor deficiency Prothrombin Complex Concentrates, Platelets with the use of platelets and Red Blood Cells for correcting hemoglobin levels

Diagnostic Test: Thromboelastometry; Drug: Fibrinogen Concentrate Human; Drug: Prothrombin Complex Concentrates; Other: Platelets; Other: Red Blood Cells

STANDARD COAGULATION TEST ALGORITHM

ACTIVE COMPARATOR

Decision to treat will be guided by standard cogulation lab test (Thrombine time, Active Thromboplastine time, Clauss fibrinogen, platelets count etc) for fribrinogen deficiency the investigators will treat with cryoprecipitates, for correction of factor deficiency fresh frozen plasma, Platelets with the use of platelets and Red Blood Cells for correcting hemoglobin levels

Diagnostic Test: Standard Coagulation Test; Other: Platelets; Other: Red Blood Cells; Other: Fresh Frozen Plasma; Other: cryoprecipitates

Interventions

Thromboelastometry DIAGNOSTIC_TEST

devices generate output by transducing changes in the viscoelastic strength of a small sample of clotting blood (300 µl) to which a constant rotational force is applied. These point of care devices allow visual assessment of blood coagulation from clot formation, through propagation, and stabilization, until clot dissolution. Computer analysis of the output allows sophisticated clot formation/dissolution kinetics and clot strength data to be generated

Also known as: ROTEM

Thromboelastometry

Standard Coagulation Test DIAGNOSTIC_TEST

coagulation tests, such as the prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT), to assess blood clotting function in patients. Clauss Fibrinogen.

Also known as: blood coagulation test

STANDARD COAGULATION TEST ALGORITHM

Fibrinogen Concentrate Human DRUG

To treat acquired fribinogen deficiency investigators will treat with the following doses FIBTEM A5 = 9-11 MM a 2 G FIBRINOGEN CONC. (25 MG/KG); FIBTEM A5 = 4-8 MM a 4 G FIBRINOGEN CONC. (50 MG/KG); FIBTEM A5 \< 4 MM a 6 G FIBRINOGEN CONC. (75 MG/KG)

Also known as: Chlotafact

Thromboelastometry

Prothrombin Complex Concentrates DRUG

to treat acquired factor deficiency investigators will treat as follows PROTROMBIN COMPLEX CONCENTRATE EXTEM CT \> 80 SEC AND FIBTEM A5 ≥ 8 MM 4F-PCC 20 IU/KG (F II, VII, IX and X) GOAL: EXTEM CT ≤ 80 SEC

Also known as: Confidex

Thromboelastometry

Platelets OTHER

PLATELETS EXTEM A5 \< 40 MM AND FIBTEM A5 ≥ 12 MM EXTEM A5 \< 40 MM → 1 PLATELET POOL OR APHERESIS; EXTEM A5 \< 30 MM → 2 PLATELET POOL OR APHERESIS GOAL: EXTEM A5: 40-50 MM or PLATELET COUNT \< 100/µL PLT \< 100/µL → 1 PLATELET POOL OR APHERESIS; PLT \> 50/µL → 2 PLATELET POOL OR APHERESIS GOAL: PLT COUNT \> 100/µL

STANDARD COAGULATION TEST ALGORITHM; Thromboelastometry

Red Blood Cells OTHER

Transfuce Red Blood Cells if Hemoglobine levels \< 7 G/DL; 1 unit of FFP for every unit of RBC Transfused GOAL: Hb \> 7.5 G/DL

Also known as: RBC

STANDARD COAGULATION TEST ALGORITHM; Thromboelastometry

Fresh Frozen Plasma OTHER

FRESH FROZEN PLASMA TP AND/OR TTP PATHOLOGICAL INR, 2.0-4.0 → FFP 20 ML/KG GOAL: TP AND TTP NORMAL AND INR \< 2.0

STANDARD COAGULATION TEST ALGORITHM

cryoprecipitates OTHER

FIBRINOGEN (CLAUSS) \< 250 MG/DL FIB 200-250 MG/DL → CRYOS, PACK OF 10 (25 MG/KG); FIB 100-200 MG/DL → CRYOS, PACK OF 20 (50 MG/KG); FIB \< 100 MG/DL → CRYOS, PACK OF 30 (75 MG/KG) GOAL: FIB \> 250 MG/DL

STANDARD COAGULATION TEST ALGORITHM

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: all female patients with severe obstetric hemorrhage (more than 1000 ml of estimated blood loss)
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with severe obstetric hemorrhage of any cause

You may not qualify if:

• obstetric hemorrhage patients derived from other hospitals Patients with less than 1000 ml of estimated blood loss those who do not want to participate in the study

Sponsors & Collaborators

• Angel Augusto Perez Calatayud: lead
• Grupo Mexicano para el Estudio de la Medicina Intensiva: collaborator

Study Sites (1)

Hospital de Especialidades Del Niño Y La Mujer

Querétaro City, Querétaro, 76090, Mexico

Location

Related Publications (12)

• Mallaiah S, Barclay P, Harrod I, Chevannes C, Bhalla A. Introduction of an algorithm for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage. Anaesthesia. 2015 Feb;70(2):166-75. doi: 10.1111/anae.12859. Epub 2014 Oct 7.

  PMID: 25289791 BACKGROUND

• Mallaiah S, Chevannes C, McNamara H, Barclay P. A reply. Anaesthesia. 2015 Jun;70(6):760-1. doi: 10.1111/anae.13128. No abstract available.

  PMID: 25959192 BACKGROUND

• Collins PW, Cannings-John R, Bruynseels D, Mallaiah S, Dick J, Elton C, Weeks AD, Sanders J, Aawar N, Townson J, Hood K, Hall JE, Collis RE. Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial. Br J Anaesth. 2017 Sep 1;119(3):411-421. doi: 10.1093/bja/aex181.

  PMID: 28969312 BACKGROUND

• Wikkelso AJ, Edwards HM, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, Hanke G, Secher EL, Sharif HF, Pedersen LM, Troelstrup A, Lauenborg J, Mitchell AU, Fuhrmann L, Svare J, Madsen MG, Bodker B, Moller AM; FIB-PPH trial group. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial. Br J Anaesth. 2015 Apr;114(4):623-33. doi: 10.1093/bja/aeu444. Epub 2015 Jan 13.

  PMID: 25586727 BACKGROUND

• Snegovskikh D, Souza D, Walton Z, Dai F, Rachler R, Garay A, Snegovskikh VV, Braveman FR, Norwitz ER. Point-of-care viscoelastic testing improves the outcome of pregnancies complicated by severe postpartum hemorrhage. J Clin Anesth. 2018 Feb;44:50-56. doi: 10.1016/j.jclinane.2017.10.003. Epub 2017 Nov 7.

  PMID: 29121548 BACKGROUND

• Olde Engberink RH, Kuiper GJ, Wetzels RJ, Nelemans PJ, Lance MD, Beckers EA, Henskens YM. Rapid and correct prediction of thrombocytopenia and hypofibrinogenemia with rotational thromboelastometry in cardiac surgery. J Cardiothorac Vasc Anesth. 2014 Apr;28(2):210-6. doi: 10.1053/j.jvca.2013.12.004.

  PMID: 24630470 BACKGROUND

• Song JG, Jeong SM, Jun IG, Lee HM, Hwang GS. Five-minute parameter of thromboelastometry is sufficient to detect thrombocytopenia and hypofibrinogenaemia in patients undergoing liver transplantation. Br J Anaesth. 2014 Feb;112(2):290-7. doi: 10.1093/bja/aet325. Epub 2013 Sep 24.

  PMID: 24065728 BACKGROUND

• Collins PW, Lilley G, Bruynseels D, Laurent DB, Cannings-John R, Precious E, Hamlyn V, Sanders J, Alikhan R, Rayment R, Rees A, Kaye A, Hall JE, Paranjothy S, Weeks A, Collis RE. Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study. Blood. 2014 Sep 11;124(11):1727-36. doi: 10.1182/blood-2014-04-567891. Epub 2014 Jul 14.

  PMID: 25024304 BACKGROUND

• Hagemo JS, Christiaans SC, Stanworth SJ, Brohi K, Johansson PI, Goslings JC, Naess PA, Gaarder C. Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study. Crit Care. 2015 Mar 23;19(1):97. doi: 10.1186/s13054-015-0823-y.

  PMID: 25888032 BACKGROUND

• Baksaas-Aasen K, Van Dieren S, Balvers K, Juffermans NP, Naess PA, Rourke C, Eaglestone S, Ostrowski SR, Stensballe J, Stanworth S, Maegele M, Goslings JC, Johansson PI, Brohi K, Gaarder C; TACTIC/INTRN collaborators. Data-driven Development of ROTEM and TEG Algorithms for the Management of Trauma Hemorrhage: A Prospective Observational Multicenter Study. Ann Surg. 2019 Dec;270(6):1178-1185. doi: 10.1097/SLA.0000000000002825.

  PMID: 29794847 BACKGROUND

• Mace H, Lightfoot N, McCluskey S, Selby R, Roy D, Timoumi T, Karkouti K. Validity of Thromboelastometry for Rapid Assessment of Fibrinogen Levels in Heparinized Samples During Cardiac Surgery: A Retrospective, Single-center, Observational Study. J Cardiothorac Vasc Anesth. 2016 Jan;30(1):90-5. doi: 10.1053/j.jvca.2015.04.030. Epub 2015 May 5.

  PMID: 26296822 BACKGROUND

• Perez-Calatayud AA, Briones-Garduno JC, Rojas-Arellano ML. [Use of thromboelastography and thromboelastometry for the rational and opportune transfusion of hemoderivatives in obstetric hemorrhage]. Ginecol Obstet Mex. 2015 Sep;83(9):569-77. Spanish.

  PMID: 26591047 RESULT

MeSH Terms

Conditions

Postpartum Hemorrhage; Disseminated Intravascular Coagulation

Interventions

Thrombelastography; Blood Coagulation Tests; Fibrinogen; prothrombin complex concentrates; Platelet Count; Erythrocyte Count

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Thrombophilia

Intervention Hierarchy (Ancestors)

Hematologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors; Blood Cell Count; Cell Count; Cytological Techniques; Platelet Function Tests; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Angel Augusto Perez Calatayud, M.D.

  Head Obstetric ICU

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head Intensive Care Unit Hospital de Especialidades del Niño y la Mujer Dr Felipe Nuñez Lara

Model Details: Group A Fibrinogen Concentrate, Protrombin Complex Concentrate, trhromboelastometry guided Group B Cryoprecipitates, fresh frozen plasma, standard coagulation lab test

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 24, 2018
• Study Start: November 1, 2018
• Primary Completion: November 30, 2020
• Study Completion: December 30, 2020
• Last Updated: June 8, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: after recruiting 50% of the participants and it will be available always
• Access Criteria: open

Locations

ME (1)