Feasibility and Safety of Immunoglobulin (Ig) Prophylactic Treatment in COPD Patients With Frequent Exacerbations: A Pilot Study
| Registry | NCT02690038 |
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| Status | Completed |
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| Phase | Phase 2 |
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| Study type | Interventional; randomized, parallel, masking: triple, other |
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| Enrollment | 48 (Actual) |
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| Sponsor | Ottawa Hospital Research Institute (Other); collaborators: CSL Behring, Grifols Biologicals, LLC |
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| Conditions | Chronic Obstructive Pulmonary Disease |
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| Interventions | Intravenous immunoglobulin (IVIG), Normal Saline (Drug) |
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| Dates | start 2016-09-01, primary completion 2019-11-20, completion 2019-11-20, first posted 2016-02-24, last updated 2019-11-27 |
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| Locations | 1 site in Canada |
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Related Papers Related Patents Related Grants Related Experts
All trials for Chronic Obstructive Pulmonary Disease All trials of Intravenous immunoglobulin (IVIG) All trials of Normal Saline
-Summary
This study will look at immunoglobulin (Ig) treatment in hospitalized chronic obstructive lung disease (COPD) patients with frequent exacerbations.
This is a Phase II, pilot randomized double blind control study, meaning this study will help assess if this research can be expanded to evaluate Ig treatment in patients with COPD. Ig treatment is a sterile solution of human immunoglobulin proteins given intravenously (in the vein). Immunoglobulins are part of the immune system and help the body fight infections. Participants will be assigned to either receiving the Ig treatment or normal saline as a control product every 4 weeks for 12 months.
Participants will continue on current standard therapy as determined by their treating physician.
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+Arms and interventions
| Arm | Type | Interventions | Description |
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| Intervention Arm 1: Treatment | Experimental | Drug: Intravenous immunoglobulin (IVIG) | Baseline Ig < 7g/L group - Intravenous immunoglobulin (IVIG) 0.8 g/kg will be given within 12 hours after randomization during hospital admission and then every 4 weeks for 44 weeks (total 48 weeks).
Baseline Ig > or = 7 g/L group - Intravenous immunoglobulin (IVIG) 0.5 g/kg will be given within 12 hours after randomization during hospital admission and then every 4 weeks for 44 weeks (total 48 weeks). |
| Intervention Arm 2: Control | Active comparator | Drug: Normal Saline | Baseline Ig < 7g/L group - Normal Saline (0.9% NaCl) 8 mL/kg will be given within 12 hours after randomization during hospital admission and then every 4 weeks for 44 weeks (total 48 weeks).
Baseline Ig > or = 7 g/L group - Normal Saline (0.9% NaCl) 5 mL/kg will be given within 12 hours after randomization during hospital admission and then every 4 weeks for 44 weeks (total 48 weeks). |
- Intravenous immunoglobulin (IVIG) (Drug), also known as Gamunex, CBS IGIV-nex, Privigen, Octagam: Baseline Ig < 7g/L group - Intravenous immunoglobulin (IVIG) 0.8 g/kg will be given within 12 hours after randomization.
Baseline Ig > or = 7 g/L group - Intravenous immunoglobulin (IVIG) 0.5 g/kg will be given within 12 hours after randomization
- Normal Saline (Drug), also known as Saline, Sodium Chloride: Baseline Ig < 7g/L group - Normal Saline (0.9% NaCl) 8 mL/kg will be given within 12 hours after randomization.
Baseline Ig > or = 7 g/L group - Normal Saline (0.9% NaCl) 5 mL/kg will be given within 12 hours after randomization
+Outcome measures
Primary outcomes
- Recruitment [52 weeks]: Average number of patients being recruited per month. The study meets primary outcome if at least 4 patients can be recruited per month on average.
- Adherence and protocol compliance [104 weeks]: Number and percentage of recruited patients adhere to the allocated treatment and protocol. We aim to achieve 80% adherence rate which is defined as at least 80% of patients adhere to 80% of allocated treatment and protocol
Secondary outcomes
- Number of participants with treatment-related adverse events as assessed by CTCAE [104 weeks]: This will be assessed by documentation of adverse events in patients treated with Ig treatment versus control
- Tolerability of treatment [104 weeks]: The proportion of patients able to complete the treatment in the experimental arm during the study period versus in the control arm
- Efficacy trend: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) rates [104 weeks]: AECOPD will be ascertained by monthly follow-up phone calls as well as questionnaires during study visits to detect inpatient/outpatient treatment for exacerbations.
- Efficacy trend: Health status [104 weeks]: measured by the validated St. George Respiratory Questionnaire
- Efficacy trend: Quality of life [104 weeks]: validated quality of life measurement tool - EuroWol EQ-5D-5L
- Efficacy trend: % predicted FEV1 [104 weeks]: FEV1 value will be measured using a hand held spirometer. FEV1 value will be recorded in Litres (L) and reported as a percent of their predicted value (using the NHANES III reference standards for predicted values
- Efficacy trend: FEV1/FVC [104 weeks]: FVC will be measured using a hand held spirometer, and will be recorded in Litres (L). Ratio of FEV1 and FVC will be reported.
- Efficacy trend: Health services use [104 weeks]: Number of non-study physician visits, emergency department (ED) and hospital admissions over the twelve-month study period.
- Efficacy trend: Health care system cost [104 weeks]: we will take the perspective of healthcare system and will measure the cost of health services use and an intervention. Intervention cost includes medication, staff, and equipment cost.
+Eligibility
Sex: All, ages: 40 Years to any
Inclusion Criteria:
* Hospitalized adult patient with AECOPD (clinically dominant AECOPD in the case of multiple co-morbidities eg. absence of overt lobar pneumonia or acute congestive heart failure or alternate diagnosis such as acute coronary syndrome or pulmonary embolism)
* Diagnosis of severe COPD (post bronchodilator FEV1 <50%, FEV1/FVC ratio <0.7) made by standard spirometry within previous 12 months or within three days of admission if previous PFT data is not available
* Age >40 years
* >10 pack year smoking history
* At least one COPD exacerbation in the previous 12 months before enrollment, defined by having had documented inpatient or outpatient treatment by physician with antibiotics and/or prednisone for physician diagnosed COPD exacerbation
* Expected to live > 12 months
Exclusion Criteria:
* Known severe hypersensitivity to immunoglobulin or its components (anaphylaxis)
* Underlying malignancy (including chronic lymphocytic leukemia)
* History of hematopoietic stem cell transplant or solid organ transplant
* Current treatment with a biological therapy for other conditions
* Concomitant significant immunodeficiency or on immunosuppressive treatment other than for COPD
* Alpha-1 antitrypsin deficiency
* Significant proteinuria (dipstick proteinuria ≥ 3+ or known urinary protein loss ≥ 2 g/day or nephrotic syndrome) and/or has acute renal failure and/or severe renal impairment (creatinine more than 2.5 times the upper limit of normal and/or on dialysis)
* IgA deficiency (IgA <0.1 g/L)
* Immunoglobulin therapy in the last 12 months or on current Ig therapy or have a clinical indication for Ig replacement therapy (www.nacblood.ca/resources/guidelines/IVIG.html)
* Obesity (BMI ≥35 kg/m²)
* Pregnancy
+Locations (1)
| Facility | City | Country | Status |
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| The Ottawa Hospital, General Campus | Ottawa, Ontario | Canada | |
+Publications
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- Kawano T, Matsuse H, Obase Y, Kondo Y, Machida I, Tomari S, Mitsuta K, Fukushima C, Shimoda T, Kohno S. Hypogammaglobulinemia in steroid-dependent asthmatics correlates with the daily dose of oral prednisolone. Int Arch Allergy Immunol. 2002 Jul;128(3):240-3. doi: 10.1159/000064258. PMID 12119507
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- Results publication: Cowan J, Mulpuru S, Abdallah SJ, Chopra A, Purssell A, McGuinty M, Alvarez GG, Giulivi A, Corrales-Medina V, MacFadden D, Boyle L, Hasimja D, Thavorn K, Mallick R, Aaron SD, Cameron DW. A Randomized Double-Blind Placebo-Control Feasibility Trial of Immunoglobulin Treatment for Prevention of Recurrent Acute Exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2021 Dec 3;16:3275-3284. doi: 10.2147/COPD.S338849. eCollection 2021. PMID 34887657
- Results publication: Cowan J, Mulpuru S, Aaron S, Alvarez G, Giulivi A, Corrales-Medina V, Thiruganasambandamoorthy V, Thavorn K, Mallick R, Cameron DW. Study protocol: a randomized, double-blind, parallel, two-arm, placebo control trial investigating the feasibility and safety of immunoglobulin treatment in COPD patients for prevention of frequent recurrent exacerbations. Pilot Feasibility Stud. 2018 Aug 11;4:135. doi: 10.1186/s40814-018-0327-z. eCollection 2018. PMID 30116551
+Investigators