Condition
Hereditary Angioedema
Hereditary angioedema is a rare inherited condition in which too little working C1 inhibitor protein lets bradykinin build up, causing sudden swelling in the skin, gut, or airway. The evidence is strongest for two prescription medicines: icatibant cut symptoms by half in about 2 hours versus nearly 20 on placebo, and ecallantide improved symptoms more than placebo at 4 hours. Those trials measured relief during attacks, not supplements.
Sources: PMID 31290163
- Updated
- How we grade
- 100 studies cited
- Supplements studied
- 0
- Medicines and peptides
- 2
- Graded outcomes
- 9
No supplement studies yetWe haven’t found supplement studies for Hereditary Angioedema. The medicines and peptides studied for it are listed below.
Prescription medicines and peptides studied, for context
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Anaphylaxis Risk SAFETY CONCERN: Anaphylaxis in 3.9% of patients (10/255) in clinical trials. Most within first hour after injection. Black box warning. Must be administered by healthcare professional. Have anaphylaxis treatment available. Self-administration not recommended. | Worsens (the measure goes up) | Small effect | 201 studies | |||
Studies that measured anaphylaxis risk
| ||||||
| Symptom Improvement at 4 Hours EDEMA3 & EDEMA4 Phase 3 (n=168): Treatment outcome score at 4h significantly greater with ecallantide vs placebo (53.4 vs 8.1, P=0.003 in EDEMA4). Mean symptom complex severity score change -0.8 vs -0.4 placebo (P=0.01). Led to FDA approval. | Improves (the measure goes up) | Large effect | 200 studies | |||
Studies that measured symptom improvement at 4 hours
| ||||||
| Time to Symptom Relief EDEMA3+4 pooled analysis: Benefit apparent within 2 hours of dosing. Maintained through 24 hours. Need for rescue intervention: 14% ecallantide vs 36% placebo within 24h. Earlier treatment associated with better outcomes. | Changes; see studies | Moderate effect | 200 studies | |||
Studies that measured time to symptom relief
| ||||||
| Laryngeal Attack Efficacy Subset analysis of laryngeal attacks: Significant improvement in treatment outcome scores. Potential life-saving for airway-threatening attacks. Limited patient numbers in trials - use with close monitoring for severe attacks. | Improves (the measure goes up) | Moderate effect | 201 studies | |||
Studies that measured laryngeal attack efficacy
| ||||||
Key findings
- Anaphylaxis RiskWorsens (the measure goes up)
- Symptom Improvement at 4 HoursImproves (the measure goes up)
- Time to Symptom ReliefChanges; see studies
Safety notes in the studies
- Black box warning.
Studies cited
100 studies from PubMed
- Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial.
- Short review of SEC, a potential dexamethasone-sparing regimen for glioblastoma: Spironolactone, ecallantide, clotrimazole.
- Self-administration of icatibant in acute attacks of Type I hereditary angioedema: A case report and review of hereditary angioedema.
- Effect of icatibant on angiotensin-converting enzyme inhibitor-induced angioedema: A meta-analysis of randomized controlled trials.
- Novel Therapies for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review of Current Evidence.
- Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks
- [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].
- [Administration of conestat alfa, human C1 esterase inhibitor and icatibant in the treatment of acute angioedema attacks in adults with hereditary angioedema due to C1 esterase inhibitor deficiency. Treatment comparison based on systematic review results].
- Icatibant for the treatment of hereditary angioedema
- A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial).
- Ecallantide for treatment of acute hereditary angioedema attacks: analysis of efficacy by patient characteristics
- Ecallantide (DX-88) for acute hereditary angioedema attacks: integrated analysis of 2 double-blind, phase 3 studies.
- Successful long-term treatment with the bradykinin B2 receptor antagonist icatibant in a patient with hereditary angioedema
- Randomized placebo-controlled trial of the bradykinin B₂ receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial
- Response to ecallantide treatment of acute attacks of hereditary angioedema based on time to intervention: results from the EDEMA clinical trials
- Ecallantide for the treatment of hereditary angiodema in adults
- Icatibant for hereditary angioedema
- Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema
- EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema
- Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant
- Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant)
- Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor
- Novel pharmacotherapy of acute hereditary angioedema with bradykinin B2-receptor antagonist icatibant
- Comparison of therapeutic effects of garlic and d-Penicillamine in patients with chronic occupational lead poisoning
- Effect of Beetroot Juice Supplementation on Aerobic Capacity in Female Athletes: A Randomized Controlled Study.
- Effects of Low-Level Laser Therapy on Muscular Performance and Soreness Recovery in Athletes: A Meta-analysis of Randomized Controlled Trials.
- Effect of New Zealand blueberry consumption on recovery from eccentric exercise-induced muscle damage
- Effects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: A systematic review and meta-analysis.
- Time-restricted feeding plus resistance training in active females: a randomized trial
- Effects of garlic consumption on physiological variables and performance during exercise in hypoxia
- Effect of fatiguing bicycle exercise on thyroid hormone and testosterone levels in sedentary males supplemented with oral zinc
- Ingestion of casein and whey proteins result in muscle anabolism after resistance exercise
- Whey and casein labeled with L-1-13Cleucine and muscle protein synthesis: effect of resistance exercise and protein ingestion
- Changes in antioxidant status and cardiovascular risk factors of overweight young men after six weeks supplementation of whey protein isolate and resistance training
- The effect of resistance training combined with timed ingestion of protein on muscle fiber size and muscle strength
- Whey Protein Before and During Resistance Exercise Has No Effect on Muscle Mass and Strength in Untrained Young Adults
- A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy
- Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adults
- No effect of antioxidant supplementation on muscle performance and blood redox status adaptations to eccentric training
- Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stress to eccentric exercise
- Prolonged vitamin C supplementation and recovery from eccentric exercise
- Pyridoxine (B6) suppresses the rise in prolactin and increases the rise in growth hormone induced by exercise
- Effect of elk velvet antler supplementation on the hormonal response to acute and chronic exercise in male and female rowers
- Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men
- Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes.
- Effect of Eurycoma longifolia standardised aqueous root extract-Physta ® on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study
- The effects of theaflavin-enriched black tea extract on muscle soreness, oxidative stress, inflammation, and endocrine responses to acute anaerobic interval training: a randomized, double-blind, crossover study
- Additional effects of taurine on the benefits of BCAA intake for the delayed-onset muscle soreness and muscle damage induced by high-intensity eccentric exercise
- The Effects of Spirulina Supplementation on Redox Status and Performance Following a Muscle Damaging Protocol
- Preventive effects of Spirulina platensis on skeletal muscle damage under exercise-induced oxidative stress
- No Difference Between the Effects of Supplementing With Soy Protein Versus Animal Protein on Gains in Muscle Mass and Strength in Response to Resistance Exercise
- Acidosis stimulates beta-endorphin release during exercise
- Effect of sodium bicarbonate ingestion on exhaustive resistance exercise performance
- Increased blood pH but not performance with sodium bicarbonate supplementation in elite rugby union players
- Effects of chronic NaHCO3 ingestion during interval training on changes to muscle buffer capacity, metabolism, and short-term endurance performance
- Effects of chronic bicarbonate ingestion on the performance of high-intensity work
- Influence of sodium bicarbonate ingestion on plasma ammonia accumulation during incremental exercise in man
- The effects of buffer ingestion on metabolic factors related to distance running performance
- Induced metabolic alkalosis affects muscle metabolism and repeated-sprint ability
- Effect of induced alkalosis on exhaustive leg press performance
- Metabolic and blood catecholamine responses to exercise during alkalosis
- The acute reversal of a diet-induced metabolic acidosis does not restore endurance capacity during high-intensity exercise in man
- Effects of sodium bicarbonate ingestion on prolonged intermittent exercise
- Acid-base balance during repeated bouts of exercise: influence of HCO3
- Effects of various sodium bicarbonate loading protocols on the time-dependent extracellular buffering profile
- Preventive effects of 10-day supplementation with saffron and indomethacin on the delayed-onset muscle soreness
- Effects of ginseng on secretory IgA, performance, and recovery from interval exercise
- Panax ginseng Supplementation Increases Muscle Recruitment, Attenuates Perceived Effort, and Accelerates Muscle Force Recovery After an Eccentric-Based Exercise in Athletes
- No ergogenic effect of ginseng ingestion
- Influence of dietary nitrate supplementation on human skeletal muscle metabolism and force production during maximum voluntary contractions
- Dietary nitrate supplementation improves team sport-specific intense intermittent exercise performance
- Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia
- Effect of methylsulfonylmethane supplementation on exercise - Induced muscle damage and total antioxidant capacity
- Daily L-leucine supplementation in novice trainees during a 12-week weight training program
- Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women
- Marginal iron deficiency without anemia impairs aerobic adaptation among previously untrained women
- Randomized, double-blind, placebo-controlled trial of iron supplementation in female soldiers during military training: effects on iron status, physical performance, and mood
- The Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Recovery Following Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis.
- Beta-hydroxy-beta-methylbutyrate ingestion, Part I: effects on strength and fat free mass
- Effects of calcium beta-hydroxy-beta-methylbutyrate (HMB) supplementation during resistance-training on markers of catabolism, body composition and strength
- Intramuscular adaptations to eccentric exercise and antioxidant supplementation
- Glutamine protects against increases in blood ammonia in football players in an exercise intensity-dependent way
- Ginger (Zingiber officinale) reduces muscle pain caused by eccentric exercise
- The effects of gamma-oryzanol supplementation during resistance exercise training
- The effects of fish oil and isoflavones on delayed onset muscle soreness
- Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man
- The effect of ephedra and caffeine on maximal strength and power in resistance-trained athletes
- Effect of physical training on thermogenic responses to cold and ephedrine in obesity
- Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training
- Effects of short-term dehydroepiandrosterone supplementation on body composition in young athletes
- Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men
- Creatine Supplementation and Upper Limb Strength Performance: A Systematic Review and Meta-Analysis.
- Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review and Meta-Analyses
- Acute creatine loading enhances human growth hormone secretion
- The effect of short-term creatine loading on active range of movement
- Creatine supplementation enhances muscle force recovery after eccentrically-induced muscle damage in healthy individuals
- Effect of creatine supplementation during cast-induced immobilization on the preservation of muscle mass, strength, and endurance
- Increased IGF mRNA in human skeletal muscle after creatine supplementation
- Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults
- Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training