Grifols APACHE Study
Research type
Research Study
Full title
Effects of Plasma Exchange with Human Serum Albumin 5% (PE-A 5%) on Short-term Survival in Subjects with “Acute-On-Chronic Liver Failure” (ACLF) at High Risk of Hospital Mortality.
IRAS ID
252651
Contact name
Mireia Torres
Contact email
Sponsor organisation
Instituto Grifols S.A.
Eudract number
2016-001787-10
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Lay summary of study results: Lay Title
A study to see whether a treatment called plasma exchange, using a blood protein called human albumin, can help people with long‑term liver disease who suddenly become very sick and are at high risk of dying in the hospital.
Official Title:
Effects of Plasma Exchange with Human Serum Albumin 5% (PE-A 5%) on Short-term Survival in Subjects with "Acute-On-Chronic Liver Failure" (ACLF) at High Risk of Hospital Mortality
Study Identifiers:
- IRAS 252651
- Protocol no. IG1407
- EudraCT no. 2016-001787-10
- EU CT no. 2022-502187-20-00
Sponsors
The Sponsor of this study was Instituto Grifols, S.A., Spain
General Info
This study was done to see if plasma exchange with Albutein 5% (PE-A 5%), given together with Standard Medical Treatment (SMT), could help people live longer without needing a liver transplant. The study looked at this over the first 90 days after starting the treatment, and compared the results to people who received SMT Alone. All people in the study had ACLF. This was a Phase 3 study where a new treatment is tested in a large number of people to find out if it is safe and if it works. This study started in June 2019 and ended in April 2025. A total of 274 people, ages 18 to 79, took part in the study with different grades of ACLF: ACLF-1b, ACLF-2, or ACLF-3a. The study was done in 9 countries (14 participants in Austria, 34 in Belgium, 11 in France, 31 in Germany, 31 in Italy, 5 in Portugal, 37 in Spain, 14 in the United Kingdom, and 97 in the United States).
The study was ended earlier than planned because of a decision made by the sponsor, not because of safety concerns.
The main results suggested that SMT + PE-A 5% helped people live longer without a liver transplant during the 90-day period compared to SMT Alone.
Study Treatments
Albutein 5% was the treatment studied in this research, given to patients through an infusion (a slow drip into a vein). Albutein 5% is made from human plasma. It contains albumin, an important protein found in blood.
People with ACLF were placed into one of the two groups by chance (this is called randomization and helps make the groups more equal, making the results more trustworthy). One group received SMT + PEA 5%, the other received SMT Alone. Of the 274 people, 7 did not receive either study treatment, 128 received SMT + PE-A 5%, and 139 received SMT Alone.
Side effects
The researchers wrote down any medical problems that people had during the study. Some medical problems may have happened for reasons not related to the study treatment, such as another illness the person already had. Other medical problems may have been caused by the study treatment. By comparing medical problems in the group that got the study treatment with the group that did not get it, the researchers can learn what side effects the treatment might cause.
If any new medical problem appeared during the study, the researchers reported it. They also reported if any medical problem someone already had became worse.
A medical problem is called “serious” when it is life-threatening, requires hospital care, or causes long-lasting health issues.
Of 128 people who received SMT + PE-A 5%, 109 people (85.2%) had at least one medical problem. Of 139 people who received SMT Alone, 100 people (71.9%) had at least one medical problem. These included:
Bladder/urine infection: SMT+PE-A 5% 13, SMT 6
Lung infection: SMT+PE-A 5% 5, SMT 12
Life-threatening infection causing low blood pressure: SMT+PE-A 5% 3, SMT 7
Coronavirus infection: SMT+PE-A 5% 2, SMT 7
Low potassium levels: SMT+PE-A 5% 18, SMT 21
Low magnesium levels: SMT+PE-A 5% 8, SMT 8
High blood sugar: SMT+PE-A 5% 8, SMT 6
Low phosphorus levels: SMT+PE-A 5% 8, SMT 5
Loose or watery stools: SMT+PE-A 5% 11, SMT 6
Stomach pain: SMT+PE-A 5% 7, SMT 6 (4.3%)
Feeling sick to the stomach: SMT+PE-A 5% 3, SMT 7
Swelling in the legs or arms: SMT+PE-A 5% 12, SMT 5
Fever: SMT+PE-A 5% 7, SMT 3
Low red blood cell count: SMT+PE-A 5% 18, SMT 11
Low blood pressure: SMT+PE-A 5% 16, SMT 10
Irregular heartbeat: SMT+PE-A 5% 7, SMT 3
Trouble sleeping: SMT+PE-A 5% 7, SMT 2
Overall, 65 out of 267 people in the study (24.3%) had serious medical problems, 37 people (28.9%) in the SMT+PE-A 5% group, and 28 people (20.1%) in the SMT Alone group. Sixteen people stopped the study because of medical problems.
119 of the 267 people (44.6%) died during the study: 49 out of 128 people (38.3%) in the SMT+PE-A 5% group and 70 out of 139 people (50.4%) in the SMT Alone group.
One person had two serious medical problems that the researchers thought might be related to the SMT+PE-A 5% treatment. This person died because of these medical problems.
Study results
Both the SMT + PE-A 5% group and the SMT Alone group were similar in age, health, and other features. In both groups, alcohol was the most common reason people developed liver cirrhosis. The SMT + PE-A 5% group helped raise and keep higher levels of albumin in the blood compared to the SMT Alone group.
The results suggest SMT + PE-A 5% treatment helped people in the study live longer without needing a liver transplant, lowered the number of deaths, and reduced problems related to their disease when compared to SMT Alone. The main goal of the study, to show that the combined treatment improved survival without a transplant after 90 days, was achieved.
The treatment was well tolerated. No new or unexpected risks were seen beyond what is already known for Albutein 5%, which is an approved albumin product, so safety concerns would not prevent the treatment from being used.
How has this study helped participants and researchers?
The study results suggest that disease progression may have improved in people who received SMT + PE-A 5% compared to those receiving SMT Alone. These results may help with developing new treatments for people with ACLF. Researchers look at the results of many studies to learn which treatments work and are safe. The results from this study can be used in other research to help find better ways to treat people with ACLF.
Are there plans for further studies?
No further Albutein 5% clinical studies are currently planned.
Where to find more info
For more details visit:
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Cnewcastlenorthtyneside2.rec%40hra.nhs.uk%7C71e83068d8f94892db5408dea4ff82db%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639129614495667640%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=wi3nWJ7AmA1jv8dkXmKyTDdlYZ2Vs7K4GHwLImCi3wA%3D&reserved=0 using study identifier 2016-001787-10
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Feuclinicaltrials.eu%2FNBTI%2F_P7EAQ%2FAQ%2F5793b433-b957-401f-a015-45d43c5cbedc%2F1%2Fy5qDvK2TYh&data=05%7C02%7Cnewcastlenorthtyneside2.rec%40hra.nhs.uk%7C71e83068d8f94892db5408dea4ff82db%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639129614495720478%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=z8JC4N59KKhWT9kmkkJG2FNUrLTwWEvNvaB5sOx52kw%3D&reserved=0 identifier 2022-502187-20-00
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Cnewcastlenorthtyneside2.rec%40hra.nhs.uk%7C71e83068d8f94892db5408dea4ff82db%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639129614495766989%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=kmDjXOGpRImSUBWg2dv2LqHPA1PgqFE6ypKF0dS8lkE%3D&reserved=0 identifier NCT03702920
Participants with questions about study results, please speak with staff at your study site.People with cirrhosis of the liver may become critically ill with acute on chronic liver failure (ACLF), where liver failure progresses and multiple other organ systems also fail. ACLF has a very high mortality and there are very few treatments that are known to be effective. The purpose of this study is to determine if Blood Plasma exchange (PE) with Albumin 5% (A) is both safe and has a beneficial effect on the progression of ACLF. PE-A is already used in other medical conditions and enables potentially toxic substances to be eliminated from the blood, whilst the plasma removed is replaced with a solution containing albumin in order to maintain cardiovascular and biochemical stability. Albumin is produced in the liver and is the most abundant protein in human plasma with an important role in maintaining blood pressure and as a transport protein for many natural substances and a variety of drugs. It is used routinely as an effective replacement fluid in many clinical conditions where blood volume must be supported, including in patients with cirrhosis. Its use in PE-A treatment may have further benefits by removing harmful albumin-bound substances and by it replacement by infusing new normal albumin. PE-A has been tested in subjects with acute liver failure, a condition that reproduces many features of ACLF, including liver failure, inflammation of body systems, multi-organ involvement and a high short-term mortality. In this condition PE-A was both safe and its use was associated with improved survival. A recent study in subjects with ACLF has also reported clinical benefits of PE with albumin. However, more data about how effective PE with albumin is in ACLF is still needed and this study aims to investigate this though its testing in a randomised clinical trial.
REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
18/NE/0311
Date of REC Opinion
10 Dec 2018
REC opinion
Further Information Favourable Opinion