A Phase 2 interventional study of Autoantibody Reductive Therapy and Treatment as Usual (TAU) in Idiopathic Pulmonary Fibrosis, Acute Fatal Form, sponsored by University of Alabama at Birmingham. Completed at 7 sites in United States. Open to participants aged 40 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-02-24.
Sponsored by University of Alabama at Birmingham · Phase 2, Interventional, and Treatment
Acute exacerbations (AE) are a dreaded manifestation of idiopathic pulmonary fibrosis (IPF) that presents with rapidly worsening respiratory function over days to weeks. AE account for about 1/2 the deaths in IPF patients, and are refractory to all medical therapies attempted to date.
Considerable preliminary data shows pathological B-cell abnormalities and autoantibodies are present in AE-IPF and associated with disease severity.
The experimental therapy here (therapeutic plasma exchange plus rituximab plus intravenous immunoglobulin) is mechanistically targeted to ameliorate autoantibody-mediated pulmonary injury. Anecdotal pilot studies indicate these treatments have significant benefit for a disease syndrome that has, until now, been almost invariably inexorable. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF.
The primary goal of clinical trial is to determine effects of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG) in comparison to effects of treatment as usual (TAU), among AE-IPF patients.
Our central hypothesis is "AUTOANTIBODY REDUCTION IS BENEFICIAL FOR AE-IPF PATIENTS." A corollary of this hypothesis is that antibody-mediated autoimmunity can play an important role in IPF exacerbations.
Following baseline screening assessments, hospitalized AE-IPF patients at the collaborating sites that meet all inclusion/exclusion criteria will be randomly assigned to receive one of the following treatments in a ratio of 2:1:
Steroids: Prednisone 60 mg (p.o.) on day 1, followed by 20 mg/day on days 2-5, 7-14, and 16-19 (or the i.v. methylprednisolone equivalent). Methyl-prednisolone 100 mg i.v. will be administered on days 6 and 15, as a premedication prior to the rituximab.
Insertion of a dialysis/apheresis catheter into a central vein, and initiation of therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG) regimens:
Therapeutic Plasma Exchange (TPE) will consist of 1x estimated plasma volume exchanges for 3 successive days (1-3) and then, after a one day interval to enable equilibration of autoantibodies between intra- and extra-vascular spaces, again on days 5, 6, 9, 11, 13, and 15.
Rituximab: One gm i.v. will be administered on day 6 and day 15 after completion of the TPE on those days.
Intravenous immunoglobulin (IVIG): 0.5 gm/kg/day i.v. on days 16-19
The same steroid regimen as described for Arm A, i.e., prednisone 60 mg (p.o.) on day 1, followed by 20 mg/day on days 2-5, 7-14, and 16-19 (or the i.v. methylprednisolone equivalent), and methylprednisolone 100 mg i.v. administered on days 6 and 15.
All patients enrolled in both cohorts at all sites will also receive empiric broad-spectrum antibiotics for 8 days. The empiric antibiotic regimen will be reassessed and tailored based on any subsequent cultures and sensitivity results.
Patients will be monitored carefully for occurrences of adverse events, laboratory test abnormalities, and changes in vital signs.
The respective treatment courses can be finished on an outpatient basis among enrolled patients who are able to be discharged from the hospital, if medically indicated, and if those treatment compliance can be assured.
Patients will be followed for the duration of their hospital admission after enrollment, and then observed as either inpatients or outpatients on days 19, 60, 90, 180, 270, and 365. A telephone contact will occur at monthly intervals, aside from those visits above. The total observation/subject is 365 days.
Exclusion Criteria:
Therapeutic Plasma Exchange (TPE) consisting of 1x estimated plasma volume exchanges for 3 successive days (1-3) and then, after a one day interval to enable equilibration of autoantibodies between intra- and extra-vascular spaces, again on days 5, 6, 9, 11, 13, and 15. Rituximab: One gm i.v. will be administered on day 6 and day 15 after completion of the TPE on those days. Intravenous immunoglobulin (IVIG): 0.5 gm/kg/day i.v. on days 16-19 All subjects in this trial, including patients in this arm, will receive identical empiric antibiotics and steroids. The steroid dose is: Prednisone 60 mg (p.o.) on day 1, followed by 20 mg/day on days 2-5, 7-14, and 16-19 (or the i.v. methylprednisolone equivalent). Methylprednisolone 100 mg i.v. will be administered on days 6 and 15, as a premedication prior to the rituximab.
Drug: Autoantibody Reductive Therapy
The same steroid regimen as described for the experimental arm, i.e., prednisone 60 mg (p.o.) on day 1, followed by 20 mg/day on days 2-5, 7-14, and 16-19 (or the i.v. methylprednisolone equivalent), and methylprednisolone 100 mg i.v. administered on days 6 and 15, as well as empiric antibiotics.
Drug: Treatment as Usual (TAU)
TPE x 9, rituximab x 2, IVIG x 4. See arm/group descriptions for additional details.
Antibiotics and steroids
Also known as: Antibiotics and steroids
%Survival
Actuarial survival
Time frame: 6 months
Percentage of Participants With a Change in Oxygen Requirements to Maintain Adequate SaO2
Changes in amount of supplemental oxygen, as liters/min or % fractional inspired oxygen concentration, required to maintain arterial oxygen concentration (SaO2) \>/=93%
Time frame: before and immediately after hospital treatment
Walk Distance
6 minute walk distance using standardized American Thoracic Society/European Respiratory Society (ATS/ERS) protocols.
Time frame: 6 months
| Milestone | Autoantibody Reductive Therapy | Treatment as Usual (TAU) |
|---|---|---|
| Started | 33 | 18 |
| Completed | 31 | 18 |
| Not completed | 2 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
Actuarial survival
| percentage of participants | Autoantibody Reductive Therapy | Treatment as Usual (TAU) |
|---|---|---|
| %Survival | 44 ± 9 | 7 ± 6 |
Changes in amount of supplemental oxygen, as liters/min or % fractional inspired oxygen concentration, required to maintain arterial oxygen concentration (SaO2) \>/=93%
| % participants with O2 reductions | Autoantibody Reductive Therapy | Treatment as Usual (TAU) |
|---|---|---|
| Percentage of Participants With a Change in Oxygen Requirements to Maintain Adequate SaO2 | 50 | 22 |
6 minute walk distance using standardized American Thoracic Society/European Respiratory Society (ATS/ERS) protocols.
| feet | Autoantibody Reductive Therapy | Treatment as Usual (TAU) |
|---|---|---|
| Walk Distance | 245 ± 347 | 133 ± 216 |
Collected over 180 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Autoantibody Reductive Therapy | 18/33 (54.5%) | 5/33 (15.2%) | 6/33 (18.2%) |
| Treatment as Usual (TAU) | 16/18 (88.9%) | 0/18 (0%) | 2/18 (11.1%) |
| Event | Autoantibody Reductive Therapy | Treatment as Usual (TAU) |
|---|---|---|
| Hematoma at plasma exchange catheter siteBlood and lymphatic system disorders | 1/33 | 0/18 |
| Transient ischemic attackNervous system disorders | 1/33 | 0/18 |
| Pulmonary EdemaRespiratory, thoracic and mediastinal disorders | 1/33 | 0/18 |
| TransaminitisHepatobiliary disorders | 1/33 | 0/18 |
| Subcortical Cerebral IschemiaNervous system disorders | 1/33 | 0/18 |
| Drug ReactionRespiratory, thoracic and mediastinal disorders | 1/33 | 0/18 |
| Event | Autoantibody Reductive Therapy | Treatment as Usual (TAU) |
|---|---|---|
| LeukocytosisBlood and lymphatic system disorders | 6/33 | 2/18 |
| RashSkin and subcutaneous tissue disorders | 4/33 | 1/18 |
| WeaknessNervous system disorders | 3/33 | 0/18 |
| HypotensionCardiac disorders | 2/33 | 1/18 |
| Age, Categorical(Participants) | Autoantibody Reductive Therapy | Treatment as Usual (TAU) | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 33 | 18 | 51 |
| Age, Continuous(years) | Autoantibody Reductive Therapy | Treatment as Usual (TAU) | Total |
|---|---|---|---|
| Mean | 70 ± 7 | 70 ± 8 | 70 ± 7 |
| Sex: Female, Male(Participants) | Autoantibody Reductive Therapy | Treatment as Usual (TAU) | Total |
|---|---|---|---|
| Female | 13 | 2 | 15 |
| Male | 20 | 16 | 36 |
| Ethnicity (NIH/OMB)(Participants) | Autoantibody Reductive Therapy | Treatment as Usual (TAU) | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 |
| Not Hispanic or Latino | 31 | 18 | 49 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Autoantibody Reductive Therapy | Treatment as Usual (TAU) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 1 |
| White | 32 | 17 | 49 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Autoantibody Reductive Therapy | Treatment as Usual (TAU) | Total |
|---|---|---|---|
| United States | 33 | 18 | 51 |
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Idiopathic Pulmonary Fibrosis→
University of Alabama at Birmingham