Patient Blood Management for Massive Obstetric Hemorrhage

Brief Title

Patient Blood Management for Massive Obstetric Hemorrhage

Official Title

ROTEM Guided and Hemostatic Drugs Algorithms vs Standard Coagulation Test and Hemocomponent for Massive Obstetric Hemorrhage

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.
    

Detailed Description

      Introduction Obstetric Hemorrhage continues to be the first cause of maternal morbidity and
      mortality around the world especially in middle to low income countries. Copying trauma
      transfusion therapies now a days algorithms have been developing for 2.1.1 transfusion in
      massive obstetric hemorrhage. Blood products, play an essential role in the management of
      these patients, either during resuscitation or definitive treatment. Early transfusion,
      defined as that required in the first 24 hours after admission, it is required in about 5%
      that enters the hospital and about 3% comes to require massive transfusion. The blood
      components are high value resources; however, its use has been shown to be a risk factor for
      infectious transfusion related immunomodulation, and noninfectious complications (TRALI,
      TACO), development of systemic inflammatory response, multiple organ failure and death. A
      liberal transfusion policy can further introduce the risk of a patient who is already
      committed.

      Patient blood management is an evidence-based, multidisciplinary approach to optimizing the
      care of patients who might need transfusion. PBM encompasses all aspects of patient
      evaluation and clinical management surrounding the transfusion decision-making process,
      including the application of appropriate indications, as well as minimization of blood loss
      and optimization of patient red cell mass.

      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.

      Randomization for the patients will be made for every obstetric patient that enters the
      obstetric ward for attention of partum, and will be asked to sign consent, and the patients
      will be selected for each group of the study. Only does that have severe PPH will be entering
      the protocol with the algorithm for management previously selected. Demographic
      caracteristics will include Ethnicity, Body weight (KG), body height (CM) and BMI at hospital
      admission, Previous deliveries, Previous Caesarean section, Pre-eclampsia during pregnancy,
      History of obstetric hemorrhage, History of other kind of hemorrhage, Onset of labor
      (spontaneous, induced, no labor) Multiple gestation (singleton, twins, triplet) Reported
      cause of obstetric hemorrhage (placenta previa, placenta accreta, placenta abruption,
      retained placenta, uterine atony, trauma, surgical bleeding Mode of delivery (spontaneous
      vaginal, instrumental vaginal , elective Caesarean section, non-elective Caesarean section)
      Baseline Hb, Hct, Plt count, Fibrinogen (Clauss), PT/INR, PTT (at hospital admission)
      Estimated blood loss at study entry (ML).

      Treatment algorithms are evidence based and the management of coagulopathy is based on treat
      first what kills fist (ATLS proposal)

      Group A:

      THROMBOELASTOMETRY-GUIDED ALGORITHM FIBRINOGEN CONCENTRATE FIBTEM A5 < 12 MM AND EXTEM A5 <
      40 MM FIBTEM A5 = 9-11 MM → 2 G FIBRINOGEN CONC. (25 MG/KG); FIBTEM A5 = 4-8 MM → 4 G
      FIBRINOGEN CONC. (50 MG/KG); FIBTEM A5 < 4 MM → 6 G FIBRINOGEN CONC. (75 MG/KG) GOAL: FIBTEM
      A5: 12-16 MM 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
      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 NO INTERVENTION FIBTEM A5 ≥ 12 MM AND EXTEM A5 ≥ 40 MM
      AND EXTEM CT > 80 SEC NO FIBRINOGEN, CRYO, PLATELETS, 4-PCC, FFP; TRANSFUSE RBC IF Hb < 7
      G/DL GOAL: Hb > 7.5 G/DL

      Group B RATIO / STANDRAD LAB TEST-GUIDED ALGORITHM CRYOPRECIPITATE 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 PLATELETS
      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 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 NO LAB RESULTS AVAILABLE
      TRANSFUSE RED BLOOD CELLS IF Hb < 7 G/DL; GIVE 1 UNIT FFP EVERY 2 UNITS OF RBC TRANSFUSED
      GOAL: Hb > 7.5 G/DL Statistical analysis Sample is calculated to known variance. The
      investigators calculated that 100 women will be needed to provide 80% power at the two-sided
      5% level to detect a difference of total allogeneic units between groups. With a total of 100
      patients 50 in each arm, with a first revision of results after recruiting 50 patients (25 in
      each arm). 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). For continuous outcomes, a linear regression model
      will be performed and results presented as difference in adjusted means (arm A vs arm B)
      alongside 95% CIs. Count data will be analysed using Poisson multilevel or negative binomial
      models if over-dispersion is evident and presented as incident rate ratios (IRRs).

      Objectives

      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:

      Compare between the two arms Number of packs of Cryo (pack of 5 ~ 1 G Fibrinogen), Fibrinogen
      Concentrate (G), and PCC (500 UI) administered intra-op, within 24h after screening and
      in-hospital Incidence ≥ 5 U RBC transfused (first 24h after screening) Incidence ≥ 10 U RBC
      transfused (first 24h after screening) Incidence of RBC, Platelets, FFP, Cryo, Fibrinogen
      Concentrate, and PCC transfusion/administration (intra-op, first 24h and in-hospital) Total
      volume of blood products and coagulation factor concentrates transfused/administered
      (intra-op, first 24h and in-hospital) Infusion: Crystalloid (ML) and Colloids (Type; ML)
      intra-op and within 24h after screening Overall estimated blood loss (EBL, ML) Time to
      bleeding control (time from study entry to last hemostatic intervention/transfusion)
      Incidence of coagulopathy (detected by thromboelastometry or standard coagulation laboratory
      tests) Incidence of hysterectomy Incidence of re-surgery Incidence of TACO Incidence of TRALI
      Incidence of surgical site infection or sepsis Incidence of ICU admission Length of stay
      (LOS) at ICU and hospital In-hospital mortality First post-op Hb, Hct, Plt count, Fibrinogen
      (Clauss), PT, INR, PTT (recovery room or ICU) Last Hb, Hct, Plt count, Fibrinogen (Clauss),
      PT, INR, PTT before discharge from hospital Total acquisition costs of allogeneic blood
      products and coagulation factor concentrates HYPOTHESIS. The algorithm guided by ROTEM plus
      the use of hemostatic drugs, are more efficient for the reversion of coagulopathy due to
      obstetric hemorrhage, than the standard treatment group, decrases the risk of development
      known complications, decreases the need of blood transfusions, decreases morbidity and
      mortality associated to PPH, length of stay, admissions to the intensive care unit and days
      of mechanical ventilation. Without a significant increase in costs.

      RELEVANCE AND EXPECTATIONS To offer a safe alternative in the treatment of severe obstetric
      hemorrhage, which reduces the risk of transfusion associated complications,
    


Study Type

Interventional


Primary Outcome

Number of Blood products transfused

Secondary Outcome

 Number of hemocomponents or fibrinogen concentrates needed to treat hypofibrinogenemia

Condition

Post Partum Hemorrhage

Intervention

Thromboelastometry

Study Arms / Comparison Groups

 Thromboelastometry
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

100

Start Date

November 1, 2018

Completion Date

December 30, 2020

Primary Completion Date

November 30, 2020

Eligibility Criteria

        Inclusion Criteria:

        Patients with severe obstetric hemorrhage of any cause

        Exclusion Criteria:

        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
      

Gender

Female

Ages

18 Years - 45 Years

Accepts Healthy Volunteers

No

Contacts

Angel Augusto Perez Calatayud, M.D., , 

Location Countries

Mexico

Location Countries

Mexico

Administrative Informations


NCT ID

NCT03784794

Organization ID

099/21012018/MEDCRITICAHENM


Responsible Party

Sponsor-Investigator

Study Sponsor

Angel Augusto Perez Calatayud

Collaborators

 Grupo Mexicano para el Estudio de la Medicina Intensiva

Study Sponsor

Angel Augusto Perez Calatayud, M.D., Principal Investigator, Head Obstetric ICU


Verification Date

June 2021