Clinical trial NCT03784794: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post Partum Hemorrhage
Fibrinogenolysis; Hemorrhage
Fibrinogen; Deficiency, Acquired
Massive Hemorrhage
Transfusion Related Complication
Keywords: Post Partum Hemorrhage
Massive tranfusion
Thromboelastometry
Lead sponsor: Grupo Mexicano para el Estudio de la Medicina Intensiva
Sponsor class: OTHER
Collaborators: name: Grupo Mexicano para el Estudio de la Medicina Intensiva
First posted: 2018-12-24
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group A Fibrinogen Concentrate, Protrombin Complex Concentrate, trhromboelastometry guided Group B Cryoprecipitates, fresh frozen plasma, standard coagulation lab test
Primary purpose: TREATMENT

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,

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

Primary outcomes:
measure: Number of Blood products transfused
timeFrame: 24 hrs
Secondary outcomes:
measure: Number of hemocomponents or fibrinogen concentrates needed to treat hypofibrinogenemia
timeFrame: day 0 to day 15
measure: Incidence of Red Blood Cells transfusion (RBC)
timeFrame: day 0 to day 15
measure: Incidence of Massive Red Blood Cells transfusion (RBC)
timeFrame: day 0 to day 15
measure: estimated blood loss
timeFrame: day 0 to day 15
measure: Time to bleeding control
timeFrame: 24 hrs
measure: Incidence of coagulopathy
timeFrame: day 0 to day 15
measure: Incidence of hysterectomy
timeFrame: day 0 to day 15
measure: Incidence of re-surgery
timeFrame: day 0 to day 15
measure: Incidence of Transfused associated circulatory overload
timeFrame: day 0 to day 15
measure: Incidence of surgical site infection or sepsis
timeFrame: day 0 to day 15
measure: Incidence of ICU admission
timeFrame: day 0 to day 15
measure: In-hospital mortality
timeFrame: day 0 to day 15
Other outcomes:
Locations:
city: Querétaro City
country: Mexico
facility: Hospital de Especialidades Del Niño Y La Mujer
state: Queretaro
Study officials:
affiliation: Head Obstetric ICU
name: Angel Augusto Perez Calatayud, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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