A Phase 2 interventional study of Pentaglobin in Septic Shock, sponsored by Gruppo Italiano Trapianto di Midollo Osseo. Active, not recruiting at 20 sites in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-01-06.
Sponsored by Gruppo Italiano Trapianto di Midollo Osseo · Phase 2, Interventional, and Treatment
Among 53 studies in Shock, Septic with a site in Italy — 7 open to participants now, 8 under way, none of them phase 3. Shock, Septic · Italy.
Among the 53 studies in Shock, Septic with a site in Italy, this one is the 15th largest by planned enrollment of the 30 interventional ones that give a count, is one of 6 that started in 2019, is one of 9 in phase 2, and was the 28th registered.
1,078 studies on the registry are indexed under Shock, Septic; 232 are open to participants now.
Browse Shock, Septic studies →7 of the 53 studies in Shock, Septic with a site in Italy are open now. Recruiting first, the newest first:
Regione del Veneto - AULSS n. 7 Pedemontana · Sites in Italy
Niguarda Hospital · Sites in Italy
University of Turin, Italy · Sites in Italy
Azienda Usl di Bologna · Sites in Italy
CytoSorbents, Inc · Sites in Italy, Austria, Germany and 3 more countries
A study can be open while its sites in Italy have not opened yet or have stopped. Only those recruiting at a site in Italy →
Of the 136 Shock, Septic studies recruiting now, 102 (75%) set no upper age limit and 19 (14%) stop at 75 or younger; 12 take children under 18; 13 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
53 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 2 11 · Phase 3 11 · Phase 4 3
First in 2002; this study’s year is marked. 6 started in 2019.
This study's planned enrollment of 120 is above the median of 79 across 636 interventional studies indexed under Shock, Septic.
Median enrollment 118 across the 30 interventional studies, 50 across the 23 observational. Of the 37 that completed or were terminated, 3 (8%) have results posted.
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5 of 53 have an industry lead sponsor. The 10 most frequent:
Gruppo Italiano Trapianto di Midollo Osseo is the lead sponsor of 16 studies on the registry; none are open to participants now.
Gruppo Italiano Trapianto di Midollo Osseo has 1 study filed under Shock, Septic — fewer than ten, so there is no comparison to draw.
None of the studies under way reaches primary completion within a year.
Among the 53 studies in Shock, Septic with a site in Italy, from their registry updates:
This tab as a report to print or save as PDF → With an account.
To demonstrate that the early addition of Pentaglobin to the best available antimicrobial therapy is able to reduce mortality and improve survival in neutropenic febrile acute leukemia or allo- Hematopoietic stem cell transplantation (HSCT) patients colonized by carbapenem-resistant Enterobacteriaceae or by any Pseudomonas aeruginosa.
The study will enroll adult patients suffering from acute leukemia candidate to intensive chemotherapy or patients with hematological cancers candidate to allogeneic transplant with a documented colonization or previous bloodstream infection sustained by Carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa.
Primary objective: to demonstrate that the early addition of Pentaglobin to the best available antimicrobial therapy is able to reduce mortality and improve survival in neutropenic febrile acute leukemia or allo- Hematopoietic stem cell transplantation (HSCT) patients colonized by carbapenem-resistant Enterobacteriaceae or by any Pseudomonas aeruginosa.
Secondary Objectives: to evaluate the overall impact of Pentaglobin administration in the study population concerning infectious complications and treatment-related mortality.
This study will have two co-primary endpoints:
To demonstrate a 50% reduction in 30-day mortality for carriers developing a pre-engraftment bloodstream infection sustained by carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa (earlier primary endpoint).
To increase the Overall Survival (OS) at 4 months from the start of intensive treatment in all carriers of CRE or PA compared to historical controls (later primary endpoint)
Secondary endpoint are:
OS in carriers not developing a bloodstream infection sustained by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (PA) at 4 months from the start of intensive chemotherapy or transplant Days of fever > 38.3°C within 4 months from the start of start of intensive chemotherapy or transplant Days of hospitalization within 4 months from the start of intensive chemotherapy or transplant Days of i.v. antimicrobials within 4 months from the start of intensive chemotherapy or transplant Non-relapse mortality (NRM) at 4 months from the start of intensive chemotherapy or transplant Patients will be treated according to the standard procedures, which will be decided by each Center according to local policies (e.g. chemotherapy cycles for acute leukemia, choice of conditioning regimen for allo- Hematopoietic stem cell transplantation and graft-versus-host- disease prophylaxis, anti-microbial prophylaxis).
Pre-treatment microbiological screening Before the initiation of intensive chemotherapy (within 2 weeks) patients will be screened by rectal and pharyngeal swabbing for multidrug-resistant Gram-negative bacilli, as part of routine clinical practice.
If the rectal and/or pharyngeal swabs reveal the presence of Carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa, the patient will be considered eligible for the study.
Patients with a previous documented infection (within 3 months) caused by Carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa are also considered eligible for the study regardless of the result of the rectal/pharyngeal swabs.
Treatment and management of febrile neutropenia in Carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa carriers Antimicrobial treatment active against the multidrug-resistant strain should be started in case of neutropenic fever, defined as a single oral temperature of ≥38.3°C or a temperature of ≥38.0°C sustained over a one-hour period.
At the onset of neutropenic fever and before the initiation of antimicrobial therapy at least 2 sets of blood cultures (2 bottles from a peripheral vein and 2 bottles from central venous catheter) should be performed.
Patients should receive the best available first-line therapy, usually a combination therapy, based on the in vitro susceptibility results of the pre-treatment screening swab in combination to Pentaglobin 5ml/kg over a 12h i.v. infusion for 3 consecutive days. Empirical treatment should be subsequently streamlined according to microbiological results (both positive and negative) Pentaglobin should be started within 12h from the onset of fever, regardless of the presence of hemodynamic stability.
Septic shock should be diagnosed and managed according to standard procedure The duration of the antimicrobial therapy or subsequent lines of therapy will be decided by local investigators according to clinical judgment. Cycles of Pentaglobin can be repeated according to clinician judgment (usually at least 1 week).
In this study two co-primary endpoints will be evaluated: the 30-day mortality rate for carriers developing a pre-engraftment bloodstream infection sustained by Carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa and the Overall Survival at 4 months from the start of intensive treatment in pre-treatment carriers.
In order to address the multiplicity issue, the Bonferroni method to adjust the significance level will be applied as follows:
Adaptive study design
Early primary endpoint:
30-day mortality rate for carriers developing a pre-engraftment bloodstream infection sustained by Carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa.
The test was planned to determine whether it will be possible to obtain a consistent rate of reduction in 30-day mortality for carriers developing a pre-engraftment bloodstream infection sustained by CRE or PA. In the proposal, to reject the null hypothesis that p\<=0.60 (mortality rate: 0.40) vs. the alternative hypothesis that p>=0.80 (mortality rate: 0.20) with Type I error probability (α) equal to 0.03 and 80% power (1-β), a maximum of 40 evaluable patients has to be accrued.
In the first stage of the study, 31 evaluable patients will be enrolled and the trial will be terminated if 9 or more patients died by day +30; otherwise, 9 further evaluable patients will be enrolled in the second stage.
If the total number of patients died will be less than or equal to 11, the combination therapy will not be recommended for further studies.
If the total number of patients alive at day +30 is at least 30, the treatment will be deemed worthy of further investigations.
Considering that approximately 33% of enrolled patients will be "carriers developing a pre-engraftment bloodstream infection sustained by CRE or PA", a total of 120 patients will be needed to be enrolled.
So, considering the study design, an interim analysis is planned after 31 carriers developing a pre-engraftment bloodstream infection sustained by CRE or PA.
Late primary endpoint:
Overall Survival at 4 months from the start of intensive treatment in pre-treatment Carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa carriers.
The later endpoint is the Overall Survival at 4 months. This sample size was calculated using the "Sample size tables for exact single-stage phase II design" (A'Hern RP, Statistics in Medicine 2001). Considering an expected Overall Survival at 4 months of 70% from the start of intensive treatment in pre-treatment carriers, the number of patients required to evaluate an increase on the Overall Survival from 50% (P0) to 70% (P1) with 90% power at the 2.0% significance level (one side) is 68.
So, the total number of patients to be enrolled in this study is 120, including the 68 patients needed for the later endpoint. Calculations were made using PASS software.
The Data Safety Monitoring Board will make one monitoring at 31 evaluable patients (in concomitant with the interim analysis) to ensure the safety of patients enrolled in to the study.
The end of enrollment will end based on the ad interim analysis results according to the adaptive model of the study.
Enrollment may then terminate after the interim analysis provided after recording 31 bacteremia in 31 patients with CRE or PA or when the 120th patient will be enrolled.
Each patient enrolled will have a minimum follow-up period of 4 months from transplant or start chemotherapy.
Each patient enrolled developing bacteremia sustained by Carbapenem-resistant Enterobacteriaceae or Pseudomonas aeruginosa will have a 30-day follow-up from initiation of treatment with Pentaglobin.
It is planned to complete the total enrollment (120 patients) in 2 years starting from the first patient enrolled.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Severe concomitant illness:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients should receive the best available first-line therapy, usually a combination therapy, based on the in vitro susceptibility results of the pre-treatment screening swab in combination to Pentaglobin 5ml/kg over a 12h i.v. infusion for 3 consecutive days.
Drug: Pentaglobin
Antimicrobial treatment active against the multidrug-resistant strain should be started in case of neutropenic fever (oral temperature ≥38.3°C or temperature ≥38.0°C sustained over a one-hour period). Patients should receive the best available first-line therapy, usually a combination therapy, based on the in vitro susceptibility results of the pre-treatment screening swab in combination to Pentaglobin 5ml/kg over a 12h i.v. infusion for 3 consecutive days. Empirical treatment should be subsequently streamlined according to microbiological results (both positive and negative). Pentaglobin should be started within 12h from the onset of fever, regardless of the presence of hemodynamic stability.
Sepsis-related mortality
Sepsis-related mortality is considered as the time from the onset of neutropenic fever to death caused by uncontrolled documented infection, in the absence of any other interfering cause of death
Time frame: day +30 from the onset of neutropenic fever
Overall Survival
is defined as the probability of survival irrespective of disease state at any point in time. Patients alive at their last follow-up are censored. It is analyzed by the Kaplan-Meier method, Log-Rank Test and parametric or semiparametric survival models.
Time frame: at 4 months from the start of intensive treatment
Non-Relapse Mortality
It is defined as the probability of dying without previous occurrence of a relapse, which is a competing event
Time frame: at 4 months from the start of intensive treatment.
Plan to share: No
No publications or documents are linked to this record.
Ran from Dec 2019 to primary completion in May 2024, 53 months.
Of 36 non-industry phase 2 interventional studies under Shock, Septic, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 15 and three quarters within 42. This study's 53 months is above that.
Counting every sponsor, half of 41 studies reached it within 29 months; a quarter within 15 and three quarters within 42.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Pentaglobulin
Gruppo Italiano Trapianto di Midollo Osseo